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1. Author Correction: Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Author

Kim, Sang T., Chu, Yanshuo, Misoi, Mercy, Suarez-Almazor, Maria E., Tayar, Jean H., Lu, Huifang, Buni, Maryam, Kramer, Jordan, Rodriguez, Emma, Hussain, Zulekha, Neelapu, Sattva S., Wang, Jennifer, Shah, Amishi Y., Tannir, Nizar M., Campbell, Matthew T., Gibbons, Don L., Cascone, Tina, Lu, Charles, Blumenschein, George R., Altan, Mehmet, Lim, Bora, Valero, Vincente, Loghin, Monica E., Tu, Janet, Westin, Shannon N., Naing, Aung, Garcia-Manero, Guillermo, Abdel-Wahab, Noha, Tawbi, Hussein A., Hwu, Patrick, Oliva, Isabella C. Glitza, Davies, Michael A., Patel, Sapna P., Zou, Jun, Futreal, Andrew, Diab, Adi, Wang, Linghua, and Nurieva, Roza

Published
2024
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2. Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights

Author

Sujit, Sheeba J., Aminu, Muhammad, Karpinets, Tatiana V., Chen, Pingjun, Saad, Maliazurina B., Salehjahromi, Morteza, Boom, John D., Qayati, Mohamed, George, James M., Allen, Haley, Antonoff, Mara B., Hong, Lingzhi, Hu, Xin, Heeke, Simon, Tran, Hai T., Le, Xiuning, Elamin, Yasir Y., Altan, Mehmet, Vokes, Natalie I., Sheshadri, Ajay, Lin, Julie, Zhang, Jianhua, Lu, Yang, Behrens, Carmen, Godoy, Myrna C. B., Wu, Carol C., Chang, Joe Y., Chung, Caroline, Jaffray, David A., Wistuba, Ignacio I., Lee, J. Jack, Vaporciyan, Ara A., Gibbons, Don L., Heymach, John, Zhang, Jianjun, Cascone, Tina, and Wu, Jia

Published
2024
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3. Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer

Author

Hong, Lingzhi, Aminu, Muhammad, Li, Shenduo, Lu, Xuetao, Petranovic, Milena, Saad, Maliazurina B., Chen, Pingjun, Qin, Kang, Varghese, Susan, Rinsurongkawong, Waree, Rinsurongkawong, Vadeerat, Spelman, Amy, Elamin, Yasir Y., Negrao, Marcelo V., Skoulidis, Ferdinandos, Gay, Carl M., Cascone, Tina, Gandhi, Saumil J., Lin, Steven H., Lee, Percy P., Carter, Brett W., Wu, Carol C., Antonoff, Mara B., Sepesi, Boris, Lewis, Jeff, Gibbons, Don L., Vaporciyan, Ara A., Le, Xiuning, Jack Lee, J., Roy-Chowdhuri, Sinchita, Routbort, Mark J., Gainor, Justin F., Heymach, John V., Lou, Yanyan, Wu, Jia, Zhang, Jianjun, and Vokes, Natalie I.

Published
2023
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4. Synthetic PET from CT improves diagnosis and prognosis for lung cancer: Proof of concept

Author

Salehjahromi, Morteza, Karpinets, Tatiana V., Sujit, Sheeba J., Qayati, Mohamed, Chen, Pingjun, Aminu, Muhammad, Saad, Maliazurina B., Bandyopadhyay, Rukhmini, Hong, Lingzhi, Sheshadri, Ajay, Lin, Julie, Antonoff, Mara B., Sepesi, Boris, Ostrin, Edwin J., Toumazis, Iakovos, Huang, Peng, Cheng, Chao, Cascone, Tina, Vokes, Natalie I., Behrens, Carmen, Siewerdsen, Jeffrey H., Hazle, John D., Chang, Joe Y., Zhang, Jianhua, Lu, Yang, Godoy, Myrna C.B., Chung, Caroline, Jaffray, David, Wistuba, Ignacio, Lee, J. Jack, Vaporciyan, Ara A., Gibbons, Don L., Gladish, Gregory, Heymach, John V., Wu, Carol C., Zhang, Jianjun, and Wu, Jia

Published
2024
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5. Resolving the spatial and cellular architecture of lung adenocarcinoma by multiregion single-cell sequencing

Author

Sinjab, Ansam, Han, Guangchun, Treekitkarnmongkol, Warapen, Hara, Kieko, Brennan, Patrick M, Dang, Minghao, Hao, Dapeng, Wang, Ruiping, Dai, Enyu, Dejima, Hitoshi, Zhang, Jiexin, Bogatenkova, Elena, Sanchez-Espiridion, Beatriz, Chang, Kyle, Little, Danielle R, Bazzi, Samer, Tran, Linh M, Krysan, Kostyantyn, Behrens, Carmen, Duose, Dzifa Y, Parra, Edwin R, Raso, Maria Gabriela, Solis, Luisa M, Fukuoka, Junya, Zhang, Jianjun, Sepesi, Boris, Cascone, Tina, Byers, Lauren Averett, Gibbons, Don L, Chen, Jichao, Moghaddam, Seyed Javad, Ostrin, Edwin J, Rosen, Daniel, Heymach, John V, Scheet, Paul, Dubinett, Steven M, Fujimoto, Junya, Wistuba, Ignacio I, Stevenson, Christopher S, Spira, Avrum, Wang, Linghua, and Kadara, Humam

Subjects
Biomedical and Clinical Sciences, Immunology, Rare Diseases, Lung Cancer, Lung, Genetics, Cancer, 1.1 Normal biological development and functioning, Underpinning research, Good Health and Well Being, Adenocarcinoma of Lung, CD8-Positive T-Lymphocytes, Humans, Lung Neoplasms, Single-Cell Analysis, Tumor Microenvironment, Oncology and Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and 14 multiregion normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs. LUADs also exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs. T regulatory cell phenotypes are increased in normal tissues with proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages, and inflammatory dendritic cells. We further find that the LUAD ligand-receptor interactome harbors increased expression of epithelial CD24, which mediates protumor phenotypes. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for its treatment. SIGNIFICANCE: The geospatial ecosystem of the peripheral lung and early-stage LUAD is not known. Our multiregion single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecologic evolution of LUAD from the lung that comprise high-potential targets for early interception.This article is highlighted in the In This Issue feature, p. 2355.

Published
2021

6. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial

Author

Cascone, Tina, Leung, Cheuk H., Weissferdt, Annikka, Pataer, Apar, Carter, Brett W., Godoy, Myrna C. B., Feldman, Hope, William, Jr, William N., Xi, Yuanxin, Basu, Sreyashi, Sun, Jing Jing, Yadav, Shalini S., Rojas Alvarez, Frank R., Lee, Younghee, Mishra, Aditya K., Chen, Lili, Pradhan, Monika, Guo, Haiping, Sinjab, Ansam, Zhou, Nicolas, Negrao, Marcelo V., Le, Xiuning, Gay, Carl M., Tsao, Anne S., Byers, Lauren Averett, Altan, Mehmet, Glisson, Bonnie S., Fossella, Frank V., Elamin, Yasir Y., Blumenschein, Jr, George, Zhang, Jianjun, Skoulidis, Ferdinandos, Wu, Jia, Mehran, Reza J., Rice, David C., Walsh, Garrett L., Hofstetter, Wayne L., Rajaram, Ravi, Antonoff, Mara B., Fujimoto, Junya, Solis, Luisa M., Parra, Edwin R., Haymaker, Cara, Wistuba, Ignacio I., Swisher, Stephen G., Vaporciyan, Ara A., Lin, Heather Y., Wang, Jing, Gibbons, Don L., Jack Lee, J., Ajami, Nadim J., Wargo, Jennifer A., Allison, James P., Sharma, Padmanee, Kadara, Humam, Heymach, John V., and Sepesi, Boris

Published
2023
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7. AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages

Author

Hung, Chia-Nung, Chen, Meizhen, DeArmond, Daniel T., Chiu, Cheryl H.-L., Limboy, Catherine A., Tan, Xi, Kusi, Meena, Chou, Chih-Wei, Lin, Li-Ling, Zhang, Zhao, Wang, Chiou-Miin, Chen, Chun-Liang, Mitsuya, Kohzoh, Osmulski, Pawel A., Gaczynska, Maria E., Kirma, Nameer B., Vadlamudi, Ratna K., Gibbons, Don L., Warner, Steve, Brenner, Andrew J., Mahadevan, Daruka, Michalek, Joel E., Huang, Tim H.-M., and Taverna, Josephine A.

Published
2023
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8. Archival single-cell genomics reveals persistent subclones during DCIS progression

Author

Wang, Kaile, Kumar, Tapsi, Wang, Junke, Minussi, Darlan Conterno, Sei, Emi, Li, Jianzhuo, Tran, Tuan M., Thennavan, Aatish, Hu, Min, Casasent, Anna K., Xiao, Zhenna, Bai, Shanshan, Yang, Lei, King, Lorraine M., Shah, Vandna, Kristel, Petra, van der Borden, Carolien L., Marks, Jeffrey R., Zhao, Yuehui, Zurita, Amado J., Aparicio, Ana, Chapin, Brian, Ye, Jie, Zhang, Jianjun, Gibbons, Don L., Sawyer, Ellinor, Thompson, Alastair M., Futreal, Andrew, Hwang, E. Shelley, Wesseling, Jelle, Lips, Esther H., and Navin, Nicholas E.

Published
2023
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9. Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study

Author

Saad, Maliazurina B, Hong, Lingzhi, Aminu, Muhammad, Vokes, Natalie I, Chen, Pingjun, Salehjahromi, Morteza, Qin, Kang, Sujit, Sheeba J, Lu, Xuetao, Young, Elliana, Al-Tashi, Qasem, Qureshi, Rizwan, Wu, Carol C, Carter, Brett W, Lin, Steven H, Lee, Percy P, Gandhi, Saumil, Chang, Joe Y, Li, Ruijiang, Gensheimer, Michael F, Wakelee, Heather A, Neal, Joel W, Lee, Hyun-Sung, Cheng, Chao, Velcheti, Vamsidhar, Lou, Yanyan, Petranovic, Milena, Rinsurongkawong, Waree, Le, Xiuning, Rinsurongkawong, Vadeerat, Spelman, Amy, Elamin, Yasir Y, Negrao, Marcelo V, Skoulidis, Ferdinandos, Gay, Carl M, Cascone, Tina, Antonoff, Mara B, Sepesi, Boris, Lewis, Jeff, Wistuba, Ignacio I, Hazle, John D, Chung, Caroline, Jaffray, David, Gibbons, Don L, Vaporciyan, Ara, Lee, J Jack, Heymach, John V, Zhang, Jianjun, and Wu, Jia

Published
2023
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10. Collagen promotes anti-PD-1/PD-L1 resistance in cancer through LAIR1-dependent CD8+ T cell exhaustion.

Author

Peng, David H, Rodriguez, Bertha Leticia, Diao, Lixia, Chen, Limo, Wang, Jing, Byers, Lauren A, Wei, Ying, Chapman, Harold A, Yamauchi, Mitsuo, Behrens, Carmen, Raso, Gabriela, Soto, Luisa Maren Solis, Cuentes, Edwin Roger Parra, Wistuba, Ignacio I, Kurie, Jonathan M, and Gibbons, Don L

Subjects
Lung, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Extracellular Matrix, Animals, Mice, Transgenic, Humans, Mice, Carcinoma, Lewis Lung, Lung Neoplasms, Disease Models, Animal, Collagen, Amino Acid Oxidoreductases, Receptors, Immunologic, Drug Resistance, Neoplasm, Female, Male, Proto-Oncogene Proteins p21(ras), Protein Tyrosine Phosphatase, Non-Receptor Type 6, Gene Knockdown Techniques, HEK293 Cells, Programmed Cell Death 1 Receptor, Datasets as Topic, Biomarkers, Tumor, Hepatitis A Virus Cellular Receptor 2, Antineoplastic Agents, Immunological, B7-H1 Antigen, Adenocarcinoma of Lung, RNA-Seq, Cell Line, Tumor, Transgenic, Carcinoma, Lewis Lung, Disease Models, Animal, Receptors, Immunologic, Drug Resistance, Neoplasm, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Biomarkers, Antineoplastic Agents, Immunological
Abstract

Tumor extracellular matrix has been associated with drug resistance and immune suppression. Here, proteomic and RNA profiling reveal increased collagen levels in lung tumors resistant to PD-1/PD-L1 blockade. Additionally, elevated collagen correlates with decreased total CD8+ T cells and increased exhausted CD8+ T cell subpopulations in murine and human lung tumors. Collagen-induced T cell exhaustion occurs through the receptor LAIR1, which is upregulated following CD18 interaction with collagen, and induces T cell exhaustion through SHP-1. Reduction in tumor collagen deposition through LOXL2 suppression increases T cell infiltration, diminishes exhausted T cells, and abrogates resistance to anti-PD-L1. Abrogating LAIR1 immunosuppression through LAIR2 overexpression or SHP-1 inhibition sensitizes resistant lung tumors to anti-PD-1. Clinically, increased collagen, LAIR1, and TIM-3 expression in melanoma patients treated with PD-1 blockade predict poorer survival and response. Our study identifies collagen and LAIR1 as potential markers for immunotherapy resistance and validates multiple promising therapeutic combinations.

Published
2020

11. PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma

Author

Tan, Xiaochao, Banerjee, Priyam, Pham, Edward A, Rutaganira, Florentine UN, Basu, Kaustabh, Bota-Rabassedas, Neus, Guo, Hou-Fu, Grzeskowiak, Caitlin L, Liu, Xin, Yu, Jiang, Shi, Lei, Peng, David H, Rodriguez, B Leticia, Zhang, Jiaqi, Zheng, Veronica, Duose, Dzifa Y, Solis, Luisa M, Mino, Barbara, Raso, Maria Gabriela, Behrens, Carmen, Wistuba, Ignacio I, Scott, Kenneth L, Smith, Mark, Nguyen, Khanh, Lam, Grace, Choong, Ingrid, Mazumdar, Abhijit, Hill, Jamal L, Gibbons, Don L, Brown, Powel H, Russell, William K, Shokat, Kevan, Creighton, Chad J, Glenn, Jeffrey S, and Kurie, Jonathan M

Subjects
Lung Cancer, Cancer, Lung, Rare Diseases, Adenocarcinoma of Lung, Animals, Chromosomes, Human, Pair 1, Enzyme-Linked Immunosorbent Assay, Golgi Apparatus, Humans, In Vitro Techniques, Membrane Proteins, Mice, Phosphotransferases (Alcohol Group Acceptor), X-Ray Microtomography, Biological Sciences, Medical and Health Sciences
Abstract

Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)-dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.

Published
2020

12. Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer

Author

Konen, Jessica M., Rodriguez, B. Leticia, Wu, Haoyi, Fradette, Jared J., Gibson, Laura, Diao, Lixia, Wang, Jing, Schmidt, Stephanie, Wistuba, Ignacio I., Zhang, Jianjun, and Gibbons, Don L.

Subjects
Drug resistance -- Physiological aspects, Lung cancer, Non-small cell -- Development and progression, Membrane proteins -- Physiological aspects -- Health aspects, Phospholipases -- Physiological aspects -- Health aspects, Health care industry
Abstract

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and effector tumor-infiltrating [CD8.sup.+] T cells. Pharmacological inhibition of ATX, or the downstream receptor LPAR5, in combination with anti-PD-1 was sufficient to restore the antitumor immune response and efficaciously control lung tumor growth in multiple KP tumor models. Additionally, ATX was significantly correlated with inflammatory gene signatures, including a [CD8.sup.+] cytolytic score in multiple lung adenocarcinoma patient data sets, suggesting that an activated tumor-immune microenvironment upregulates ATX and thus provides an opportunity for cotargeting to prevent acquired resistance to anti-PD-1 treatment. These data reveal the ATX/LPA axis as an immunosuppressive pathway that diminishes the immune checkpoint blockade response in lung cancer., Introduction Immune checkpoint blockade (ICB), which targets immunosuppressive axes such as PD-1/PD-L1 via specific antibody treatment, has revolutionized oncological treatment strategies in many cancer types. In particular, non-small cell lung [...]

Published
2023
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14. Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity

Author

Elamin, Yasir Y., Robichaux, Jacqulyne P., Carter, Brett W., Altan, Mehmet, Tran, Hai, Gibbons, Don L., Heeke, Simon, Fossella, Frank V., Lam, Vincent K., Le, Xiuning, Negrao, Marcelo V., Nilsson, Monique B., Patel, Anisha, Vijayan, R.S.K., Cross, Jason B., Zhang, Jianjun, Byers, Lauren A., Lu, Charles, Cascone, Tina, Feng, Lei, Luthra, Rajyalakshmi, San Lucas, Francis A., Mantha, Geeta, Routbort, Mark, Blumenschein, George, Jr., Tsao, Anne S., and Heymach, John V.

Published
2022
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15. Immunogenomic intertumor heterogeneity across primary and metastatic sites in a patient with lung adenocarcinoma

Author

Chen, Runzhe, Li, Jun, Fujimoto, Junya, Hong, Lingzhi, Hu, Xin, Quek, Kelly, Tang, Ming, Mitra, Akash, Behrens, Carmen, Chow, Chi-Wan, Jiang, Peixin, Little, Latasha D., Gumbs, Curtis, Song, Xingzhi, Zhang, Jianhua, Tan, Dongfeng, Heymach, John V., Wistuba, Ignacio, Futreal, P. Andrew, Gibbons, Don L., Byers, Lauren A., Zhang, Jianjun, and Reuben, Alexandre

Published
2022
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16. Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Author

Kim, Sang T., Chu, Yanshuo, Misoi, Mercy, Suarez-Almazor, Maria E., Tayar, Jean H., Lu, Huifang, Buni, Maryam, Kramer, Jordan, Rodriguez, Emma, Hussain, Zulekha, Neelapu, Sattva S., Wang, Jennifer, Shah, Amishi Y., Tannir, Nizar M., Campbell, Matthew T., Gibbons, Don L., Cascone, Tina, Lu, Charles, Blumenschein, George R., Altan, Mehmet, Lim, Bora, Valero, Vincente, Loghin, Monica E., Tu, Janet, Westin, Shannon N., Naing, Aung, Garcia-Manero, Guillermo, Abdel-Wahab, Noha, Tawbi, Hussein A., Hwu, Patrick, Oliva, Isabella C. Glitza, Davies, Michael A., Patel, Sapna P., Zou, Jun, Futreal, Andrew, Diab, Adi, Wang, Linghua, and Nurieva, Roza

Published
2022
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17. Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes

Author

Seth, Sahil, primary, Chen, Runzhe, additional, Liu, Yang, additional, Fujimoto, Junya, additional, Hong, Lingzhi, additional, Reuben, Alexandre, additional, Varghese, Susan, additional, Behrens, Carmen, additional, McDowell, Tina, additional, Soto, Luisa Solis, additional, Haymaker, Cara, additional, Weissferdt, Annikka, additional, Kalhor, Neda, additional, Wu, Jia, additional, Le, Xiuning, additional, Vokes, Natalie I, additional, Cheng, Chao, additional, Heymach, John V., additional, Gibbons, Don L., additional, Futreal, P. Andrew, additional, Wistuba, Ignacio I., additional, Kadara, Humam, additional, Zhang, Jianhua, additional, Moran, Cesar, additional, and Zhang, Jianjun, additional

Published
2024
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18. Case report: Molecular profiling facilitates the diagnosis of a challenging case of lung cancer with choriocarcinoma features

Author

Li, Hui, primary, Hu, Xin, additional, Ning, Matthew S., additional, Fuller, Gregory N., additional, Stewart, John M., additional, Gilliam, Jared C., additional, Wu, Jia, additional, Le, Xiuning, additional, Vaporciyan, Ara A., additional, Lee, J. Jack, additional, Gibbons, Don L., additional, Heymach, John V., additional, Futreal, Andrew, additional, and Zhang, Jianjun, additional

Published
2024
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19. Lung Cancer Models Reveal Severe Acute Respiratory Syndrome Coronavirus 2–Induced Epithelial-to-Mesenchymal Transition Contributes to Coronavirus Disease 2019 Pathophysiology

Author

Stewart, C. Allison, Gay, Carl M., Ramkumar, Kavya, Cargill, Kasey R., Cardnell, Robert J., Nilsson, Monique B., Heeke, Simon, Park, Elizabeth M., Kundu, Samrat T., Diao, Lixia, Wang, Qi, Shen, Li, Xi, Yuanxin, Zhang, Bingnan, Della Corte, Carminia Maria, Fan, Youhong, Kundu, Kiran, Gao, Boning, Avila, Kimberley, Pickering, Curtis R., Johnson, Faye M., Zhang, Jianjun, Kadara, Humam, Minna, John D., Gibbons, Don L., Wang, Jing, Heymach, John V., and Byers, Lauren Averett

Published
2021
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21. Characterization of the Immune Landscape of EGFR-Mutant NSCLC Identifies CD73/Adenosine Pathway as a Potential Therapeutic Target

Author

Le, Xiuning, Negrao, Marcelo V., Reuben, Alexandre, Federico, Lorenzo, Diao, Lixia, McGrail, Daniel, Nilsson, Monique, Robichaux, Jacqulyne, Munoz, Irene Guijarro, Patel, Sonia, Elamin, Yasir, Fan, You-Hong, Lee, Won-Chul, Parra, Edwin, Solis Soto, Luisa Maren, Chen, Runzhe, Li, Jun, Karpinets, Tatiana, Khairullah, Roohussaba, Kadara, Humam, Behrens, Carmen, Sepesi, Boris, Wang, Ruiping, Zhu, Mingrui, Wang, Linghua, Vaporciyan, Ara, Roth, Jack, Swisher, Stephen, Haymaker, Cara, Zhang, Jianhua, Wang, Jing, Wong, Kwok-Kin, Byers, Lauren A., Bernatchez, Chantale, Zhang, Jianjun, Wistuba, Ignacio I., Gibbons, Don L., Akbay, Esra A., and Heymach, John V.

Published
2021
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22. Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis

Author

Wei, Ying, Kim, Thomas J, Peng, David H, Duan, Dana, Gibbons, Don L, Yamauchi, Mitsuo, Jackson, Julia R, Le Saux, Claude J, Calhoun, Cheresa, Peters, Jay, Derynck, Rik, Backes, Bradley J, and Chapman, Harold A

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Lung, Cancer, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Aetiology, Development of treatments and therapeutic interventions, A549 Cells, Amino Acid Oxidoreductases, Animals, Drug Screening Assays, Antitumor, Enzyme Inhibitors, Epithelial-Mesenchymal Transition, Fibroblasts, Humans, Lung Neoplasms, Mice, Neoplasm Metastasis, Neoplasm Proteins, Phenols, Protein Kinase Inhibitors, Protein Serine-Threonine Kinases, Pulmonary Fibrosis, Receptor, Transforming Growth Factor-beta Type I, Receptors, Transforming Growth Factor beta, Signal Transduction, Transforming Growth Factor beta1, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

TGF-β1 signaling is a critical driver of collagen accumulation and fibrotic disease but also a vital suppressor of inflammation and epithelial cell proliferation. The nature of this multifunctional cytokine has limited the development of global TGF-β1 signaling inhibitors as therapeutic agents. We conducted phenotypic screens for small molecules that inhibit TGF-β1-induced epithelial-mesenchymal transition without immediate TGF-β1 receptor (TβR) kinase inhibition. We identified trihydroxyphenolic compounds as potent blockers of TGF-β1 responses (IC50 ~50 nM), Snail1 expression, and collagen deposition in vivo in models of pulmonary fibrosis and collagen-dependent lung cancer metastasis. Remarkably, the functional effects of trihydroxyphenolics required the presence of active lysyl oxidase-like 2 (LOXL2), thereby limiting effects to fibroblasts or cancer cells, the major LOXL2 producers. Mechanistic studies revealed that trihydroxyphenolics induce auto-oxidation of a LOXL2/3-specific lysine (K731) in a time-dependent reaction that irreversibly inhibits LOXL2 and converts the trihydrophenolic to a previously undescribed metabolite that directly inhibits TβRI kinase. Combined inhibition of LOXL2 and TβRI activities by trihydrophenolics resulted in potent blockade of pathological collagen accumulation in vivo without the toxicities associated with global inhibitors. These findings elucidate a therapeutic approach to attenuate fibrosis and the disease-promoting effects of tissue stiffness by specifically targeting TβRI kinase in LOXL2-expressing cells.

Published
2017

23. CD8+ T cells inhibit metastasis and CXCL4 regulates its function

Author

Joseph, Robiya, Soundararajan, Rama, Vasaikar, Suhas, Yang, Fei, Allton, Kendra L., Tian, Lin, den Hollander, Petra, Isgandarova, Sevinj, Haemmerle, Monika, Mino, Barbara, Zhou, Tieling, Shin, Crystal, Martinez-Paniagua, Melisa, Sahin, Aysegul A., Rodriguez-Canales, Jaime, Gelovani, Juri, Chang, Jeffrey T., Acharya, Ghanashyam, Sood, Anil K., Wistuba, Ignacio I., Gibbons, Don L., Solis, Luisa M., Barton, Michelle C., Varadarajan, Navin, Rosen, Jeffrey M., Zhang, Xiang H., and Mani, Sendurai A.

Published
2021
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24. CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma

Author

Rocha, Pedro, Salazar, Ruth, Zhang, Jiexin, Ledesma, Debora, Solorzano, Jose L., Mino, Barbara, Villalobos, Pamela, Dejima, Hitoshi, Douse, Dzifa Y., Diao, Lixia, Mitchell, Kyle Gregory, Le, Xiuning, Zhang, Jianjun, Weissferdt, Annikka, Parra-Cuentas, Edwin, Cascone, Tina, Rice, David C., Sepesi, Boris, Kalhor, Neda, Moran, Cesar, Vaporciyan, Ara, Heymach, John, Gibbons, Don L., Lee, J. Jack, Kadara, Humam, Wistuba, Ignacio, Behrens, Carmen, and Solis, Luisa Maren

Published
2021
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25. Neoadjuvant Chemotherapy Increases Cytotoxic T Cell, Tissue Resident Memory T Cell, and B Cell Infiltration in Resectable NSCLC

Author

Gaudreau, Pierre-Olivier, Negrao, Marcelo V., Mitchell, Kyle G., Reuben, Alexandre, Corsini, Erin M., Li, Jun, Karpinets, Tatiana V., Wang, Qi, Diao, Lixia, Wang, Jing, Federico, Lorenzo, Parra-Cuentas, Edwin R., Khairullah, Roohussaba, Behrens, Carmen, Correa, Arlene M., Gomez, Daniel, Little, Latasha, Gumbs, Curtis, Kadara, Humam N., Fujimoto, Junya, McGrail, Daniel J., Vaporciyan, Ara A., Swisher, Stephen G., Walsh, Garrett, Antonoff, Mara B., Weissferdt, Annikka, Tran, Hai, Roarty, Emily, Haymaker, Cara, Bernatchez, Chantale, Zhang, Jianhua, Futreal, P. Andrew, Wistuba, Ignacio I., Cascone, Tina, Heymach, John V., Sepesi, Boris, Zhang, Jianjun, and Gibbons, Don L.

Published
2021
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26. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial

Author

Cascone, Tina, William, Jr, William N., Weissferdt, Annikka, Leung, Cheuk H., Lin, Heather Y., Pataer, Apar, Godoy, Myrna C. B., Carter, Brett W., Federico, Lorenzo, Reuben, Alexandre, Khan, Md Abdul Wadud, Dejima, Hitoshi, Francisco-Cruz, Alejandro, Parra, Edwin R., Solis, Luisa M., Fujimoto, Junya, Tran, Hai T., Kalhor, Neda, Fossella, Frank V., Mott, Frank E., Tsao, Anne S., Blumenschein, Jr, George, Le, Xiuning, Zhang, Jianjun, Skoulidis, Ferdinandos, Kurie, Jonathan M., Altan, Mehmet, Lu, Charles, Glisson, Bonnie S., Byers, Lauren Averett, Elamin, Yasir Y., Mehran, Reza J., Rice, David C., Walsh, Garrett L., Hofstetter, Wayne L., Roth, Jack A., Antonoff, Mara B., Kadara, Humam, Haymaker, Cara, Bernatchez, Chantale, Ajami, Nadim J., Jenq, Robert R., Sharma, Padmanee, Allison, James P., Futreal, Andrew, Wargo, Jennifer A., Wistuba, Ignacio I., Swisher, Stephen G., Lee, J. Jack, Gibbons, Don L., Vaporciyan, Ara A., Heymach, John V., and Sepesi, Boris

Published
2021
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27. The Multifaceted Role of Neutrophils in NSCLC in the Era of Immune Checkpoint Inhibitors.

Author

Miao, Shucheng, Rodriguez, Bertha Leticia, and Gibbons, Don L.

Subjects
NEUTROPHIL lymphocyte ratio, CELL physiology, NEUTROPHILS, IMMUNOTHERAPY, CELL proliferation, CELLULAR signal transduction, TUMOR markers, IMMUNE checkpoint inhibitors, CELL lines, GENE expression, METABOLITES, LUNG cancer, CHEMOKINE receptors, IMMUNOSUPPRESSION, PHENOTYPES
Abstract

Simple Summary: Lung cancer is the leading cause of cancer-related death in the U.S. and the majority of these cases are non-small-cell lung cancer (NSCLC). While immune checkpoint inhibitors (ICIs) are initially effective, patients often develop resistance to the treatment. Tumor-associated neutrophils (TANs) play a key role in the tumor environment and immune response. The main challenge is to understand how TANs influence the effectiveness of ICI treatment. This review discusses current research on how neutrophils interact with cancer cells and other components in the tumor environment. Ongoing clinical trials are exploring treatments that target these neutrophils to improve ICI therapy in NSCLC. Lung cancer is the most common cause of cancer-related death in both males and females in the U.S. and non-small-cell lung cancer (NSCLC) accounts for 85%. Although the use of first- or second-line immune checkpoint inhibitors (ICIs) exhibits remarkable clinical benefits, resistance to ICIs develops over time and dampens the efficacy of ICIs in patients. Tumor-associated neutrophils (TANs) have an important role in modulating the tumor microenvironment (TME) and tumor immune response. The major challenge in the field is to characterize the TANs in NSCLC TME and understand the link between TAN-related immunosuppression with ICI treatment response. In this review, we summarize the current studies of neutrophil interaction with malignant cells, T-cells, and other components in the TME. Ongoing clinical trials are aimed at utilizing reagents that have putative effects on tumor-associated neutrophils, in combination with ICI. Elevated neutrophil populations and neutrophil-associated factors could be potential therapeutic targets to enhance anti-PD1 treatment in NSCLC. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Programmed Death-Ligand 1 Heterogeneity and Its Impact on Benefit From Immune Checkpoint Inhibitors in NSCLC

Author

Hong, Lingzhi, Negrao, Marcelo V., Dibaj, Seyedeh S., Chen, Runzhe, Reuben, Alexandre, Bohac, Jadi M., Liu, Xiaoke, Skoulidis, Ferdinandos, Gay, Carl M., Cascone, Tina, Mitchell, Kyle G., Tran, Hai T., Le, Xiuning, Byers, Lauren A., Sepesi, Boris, Altan, Mehmet, Elamin, Yasir Y., Fossella, Frank V., Kurie, Jonathan M., Lu, Charles, Mott, Frank E., Tsao, Anne S., Rinsurongkawong, Waree, Lewis, Jeff, Gibbons, Don L., Glisson, Bonnie S., Blumenschein, George R., Jr., Roarty, Emily B., Futreal, P. Andrew, Wistuba, Ignacio I., Roth, Jack A., Swisher, Stephen G., Papadimitrakopoulou, Vassiliki A., Heymach, John V., Lee, J. Jack, Simon, George R., and Zhang, Jianjun

Published
2020
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29. STING Pathway Expression Identifies NSCLC With an Immune-Responsive Phenotype

Author

Della Corte, Carminia M., Sen, Triparna, Gay, Carl M., Ramkumar, Kavya, Diao, Lixia, Cardnell, Robert J., Rodriguez, Bertha Leticia, Stewart, C. Allison, Papadimitrakopoulou, Vassiliki A., Gibson, Laura, Fradette, Jared J., Wang, Qi, Fan, Youhong, Peng, David H., Negrao, Marcelo V., Wistuba, Ignacio I., Fujimoto, Junya, Solis Soto, Luisa M., Behrens, Carmen, Skoulidis, Ferdinandos, Heymach, John V., Wang, Jing, Gibbons, Don L., and Byers, Lauren A.

Published
2020
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30. Phase II Trial of Concurrent Atezolizumab With Chemoradiation for Unresectable NSCLC

Author

Lin, Steven H., Lin, Yan, Yao, Luyang, Kalhor, Neda, Carter, Brett W., Altan, Mehmet, Blumenschein, George, Byers, Lauren A., Fossella, Frank, Gibbons, Don L., Kurie, Jonathan M., Lu, Charles, Simon, George, Skoulidis, Ferdinandos, Chang, Joe Y., Jeter, Melenda D., Liao, Zhongxing, Gomez, Daniel R., O’Reilly, Michael, Papadimitrakopoulou, Vali, Thall, Peter, Heymach, John V., and Tsao, Anne S.

Published
2020
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33. Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer

Author

Cascone, Tina, Weissferdt, Annikka, Godoy, Myrna C. B., William, Jr., William N., Leung, Cheuk H., Lin, Heather Y., Basu, Sreyashi, Yadav, Shalini S., Pataer, Apar, Mitchell, Kyle G., Khan, Md Abdul Wadud, Shi, Yushu, Haymaker, Cara, Solis, Luisa M., Parra, Edwin R., Kadara, Humam, Wistuba, Ignacio I., Sharma, Padmanee, Allison, James P., Ajami, Nadim J., Wargo, Jennifer A., Jenq, Robert R., Gibbons, Don L., Lee, J. Jack, Swisher, Stephen G., Vaporciyan, Ara A., Heymach, John V., and Sepesi, Boris

Published
2021
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35. A collagen glucosyltransferase drives lung adenocarcinoma progression in mice

Author

Guo, Hou-Fu, Bota-Rabassedas, Neus, Terajima, Masahiko, Leticia Rodriguez, B., Gibbons, Don L., Chen, Yulong, Banerjee, Priyam, Tsai, Chi-Lin, Tan, Xiaochao, Liu, Xin, Yu, Jiang, Tokmina-Roszyk, Michal, Stawikowska, Roma, Fields, Gregg B., Miller, Mitchell D., Wang, Xiaoyan, Lee, Juhoon, Dalby, Kevin N., Creighton, Chad J., Phillips, Jr, George N., Tainer, John A., Yamauchi, Mitsuo, and Kurie, Jonathan M.

Published
2021
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36. Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer

Author

Chen, Ming, Chen, Runzhe, Jin, Ying, Li, Jun, Hu, Xin, Zhang, Jiexin, Fujimoto, Junya, Hubert, Shawna M., Gay, Carl M., Zhu, Bo, Tian, Yanhua, McGranahan, Nicholas, Lee, Won-Chul, George, Julie, Hu, Xiao, Chen, Yamei, Wu, Meijuan, Behrens, Carmen, Chow, Chi-Wan, Pham, Hoa H. N., Fukuoka, Junya, Wu, Jia, Parra, Edwin Roger, Little, Latasha D., Gumbs, Curtis, Song, Xingzhi, Wu, Chang-Jiun, Diao, Lixia, Wang, Qi, Cardnell, Robert, Zhang, Jianhua, Wang, Jing, Le, Xiuning, Gibbons, Don L., Heymach, John V., Jack Lee, J., William, Jr, William N., Cheng, Chao, Glisson, Bonnie, Wistuba, Ignacio, Andrew Futreal, P., Thomas, Roman K., Reuben, Alexandre, Byers, Lauren A., and Zhang, Jianjun

Published
2021
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37. 18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer

Author

Mitchell, Kyle G., Amini, Behrang, Wang, Yunfei, Carter, Brett W., Godoy, Myrna C. B., Parra, Edwin R., Behrens, Carmen, Villalobos, Pamela, Reuben, Alexandre, Lee, J. Jack, Weissferdt, Annikka, Moran, Cesar A., Fujimoto, Junya, Sepesi, Boris, Walsh, Garrett L., Vaporciyan, Ara A., Hofstetter, Wayne L., William, Jr., William N., Gibbons, Don L., Wang, Jing, Hwu, Patrick, Swisher, Stephen G., Piwnica-Worms, David, Kadara, Humam, Wistuba, Ignacio I., Heymach, John V., Peng, Weiyi, and Cascone, Tina

Published
2020
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38. PD-L1 Expression, Tumor Mutational Burden, and Cancer Gene Mutations Are Stronger Predictors of Benefit from Immune Checkpoint Blockade than HLA Class I Genotype in Non–Small Cell Lung Cancer

Author

Negrao, Marcelo V., Lam, Vincent K., Reuben, Alexandre, Rubin, Maria Laura, Landry, Lara Lacerda, Roarty, Emily B., Rinsurongkawong, Waree, Lewis, Jeff, Roth, Jack A., Swisher, Stephen G., Gibbons, Don L., Wistuba, Ignacio I., Papadimitrakopoulou, Vassiliki, Glisson, Bonnie S., Blumenschein, George R., Jr., Lee, J. Jack, Heymach, John V., and Zhang, Jianjun

Published
2019
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39. Case report: Molecular profiling facilitates the diagnosis of a challenging case of lung cancer with choriocarcinoma features.

Author

Hui Li, Xin Hu, Ning, Matthew S., Fuller, Gregory N., Stewart, John M., Gilliam, Jared C., Jia Wu, Xiuning Le, Vaporciyan, Ara A., Lee, J. Jack, Gibbons, Don L., Heymach, John V., Futreal, Andrew, and Jianjun Zhang

Subjects
CHORIOCARCINOMA, LUNG cancer, GERM cell tumors, DIAGNOSIS, BRAIN metastasis, TRANSCRIPTOMES
Abstract

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as "metastatic choriocarcinoma" (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of "adenocarcinoma with aberrant expression of β-hCG" and finally pathologists at our hospital, who gave the diagnosis of "poorly differentiated carcinoma with choriocarcinoma features". Genomic profiling detected a KRAS G13R mutation and transcriptomics profiling was suggestive of lung origin. The patient was treated with carboplatin/paclitaxel/ipilimumab/nivolumab followed by consolidation radiation therapy. She had no evidence of progression to date, 16 months after the initial presentation. The molecular profiling could facilitate diagnosing of challenging cancer cases. In addition, chemoimmunotherapy and local consolidation radiation therapy may provide promising therapeutic options for patients with lung cancer exhibiting choriocarcinoma features. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Clinical Benefit from Docetaxel +/− Ramucirumab Is Not Associated with Mutation Status in Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed on Platinum Doublets and Immunotherapy.

Author

Qin, Kang, Wang, Kaiwen, Li, Shenduo, Hong, Lingzhi, Padmakumar, Priyadharshini, Waree, Rinsurongkawong, Hubert, Shawna M., Le, Xiuning, Vokes, Natalie, Rai, Kunal, Vaporciyan, Ara, Gibbons, Don L., Heymach, John V., Lee, J. Jack, Woodman, Scott E., Chung, Caroline, Jaffray, David A., Altan, Mehmet, Lou, Yanyan, and Zhang, Jianjun

Subjects
THERAPEUTIC use of antineoplastic agents, DOCETAXEL, PEARSON correlation (Statistics), RESEARCH funding, T-test (Statistics), DATA analysis, IMMUNOTHERAPY, FISHER exact test, DESCRIPTIVE statistics, MULTIVARIATE analysis, MANN Whitney U Test, CHI-squared test, METASTASIS, MONOCLONAL antibodies, IMMUNE checkpoint inhibitors, KAPLAN-Meier estimator, LOG-rank test, DRUG efficacy, RESEARCH, STATISTICS, LUNG cancer, GENETIC mutation, DATA analysis software, CONFIDENCE intervals, DRUG tolerance, PROPORTIONAL hazards models
Abstract

Simple Summary: Docetaxel +/− ramucirumab is now frequently used as the standard chemotherapeutic regimen for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs), regardless of the tumor histology. However, these regimens only lead to short-lived disease control with substantial toxicity, and there is an unmet need for more treatment options in this setting. Our study investigated whether the cancer gene mutation status is associated with clinical benefits from docetaxel +/− ramucirumab by analyzing treatment and outcomes by genomic status. We also explored whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. The results of this study showed that the benefit from docetaxel +/− ramucirumab was not dependent on the cancer gene mutation status. Our exploratory analysis also suggested that platinum-/taxane-based regimens could be reasonable alternative treatment options with better efficacy and comparable tolerability. Docetaxel +/− ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/− ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/− ramucirumab n = 381 ; platinum/taxane-based regimens n = 73 ). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/− ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/− ramucirumab, the top mutated cancer genes included TP53 (n = 167) , KRAS (n = 127) , EGFR (n = 65) , STK11 (n = 32) , ERBB2 (HER2) (n = 26) , etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20–14.80 m versus 8.40 m, 95% Cl: 7.12–9.68 m, LogRank P = 0.019 ) than docetaxel +/− ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/− ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/− ramucirumab in this patient population. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Automated Cellular-Level Dual Global Fusion of Whole-Slide Imaging for Lung Adenocarcinoma Prognosis

Author

Diao, Songhui, primary, Chen, Pingjun, additional, Showkatian, Eman, additional, Bandyopadhyay, Rukhmini, additional, Rojas, Frank R., additional, Zhu, Bo, additional, Hong, Lingzhi, additional, Aminu, Muhammad, additional, Saad, Maliazurina B., additional, Salehjahromi, Morteza, additional, Muneer, Amgad, additional, Sujit, Sheeba J., additional, Behrens, Carmen, additional, Gibbons, Don L., additional, Heymach, John V., additional, Kalhor, Neda, additional, Wistuba, Ignacio I., additional, Solis Soto, Luisa M., additional, Zhang, Jianjun, additional, Qin, Wenjian, additional, and Wu, Jia, additional

Published
2023
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42. Multiomics profiling of primary lung cancers and distant metastases reveals immunosuppression as a common characteristic of tumor cells with metastatic plasticity

Author

Lee, Won-Chul, Reuben, Alexandre, Hu, Xin, McGranahan, Nicholas, Chen, Runzhe, Jalali, Ali, Negrao, Marcelo V., Hubert, Shawna M., Tang, Chad, Wu, Chia-Chin, Lucas, Anthony San, Roh, Whijae, Suda, Kenichi, Kim, Jihye, Tan, Aik-Choon, Peng, David H., Lu, Wei, Tang, Ximing, Chow, Chi-Wan, Fujimoto, Junya, Behrens, Carmen, Kalhor, Neda, Fukumura, Kazutaka, Coyle, Marcus, Thornton, Rebecca, Gumbs, Curtis, Li, Jun, Wu, Chang-Jiun, Little, Latasha, Roarty, Emily, Song, Xingzhi, Lee, J. Jack, Sulman, Erik P., Rao, Ganesh, Swisher, Stephen, Diao, Lixia, Wang, Jing, Heymach, John V., Huse, Jason T., Scheet, Paul, Wistuba, Ignacio I., Gibbons, Don L., Futreal, P. Andrew, Zhang, Jianhua, Gomez, Daniel, and Zhang, Jianjun

Published
2020
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43. Correction to: CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma

Author

Rocha, Pedro, Salazar, Ruth, Zhang, Jiexin, Ledesma, Debora, Solorzano, Jose L., Mino, Barbara, Villalobos, Pamela, Dejima, Hitoshi, Douse, Dzifa Y., Diao, Lixia, Mitchell, Kyle Gregory, Le, Xiuning, Zhang, Jianjun, Weissferdt, Annikka, Parra-Cuentas, Edwin, Cascone, Tina, Rice, David C., Sepesi, Boris, Kalhor, Neda, Moran, Cesar, Vaporciyan, Ara, Heymach, John, Gibbons, Don L., Lee, J. Jack, Kadara, Humam, Wistuba, Ignacio, Behrens, Carmen, and Solis, Luisa Maren

Published
2021
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44. EMT activates exocytotic Rabs to coordinate invasion and immunosuppression in lung cancer

Author

Xiao, Guan-Yu, primary, Tan, Xiaochao, additional, Rodriguez, Bertha L., additional, Gibbons, Don L., additional, Wang, Shike, additional, Wu, Chao, additional, Liu, Xin, additional, Yu, Jiang, additional, Vasquez, Mayra E., additional, Tran, Hai T., additional, Xu, Jun, additional, Russell, William K., additional, Haymaker, Cara, additional, Lee, Younghee, additional, Zhang, Jianjun, additional, Solis, Luisa, additional, Wistuba, Ignacio I., additional, and Kurie, Jonathan M., additional

Published
2023
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45. Targeting immunosuppressive Ly6C+ classical monocytes reverses anti-PD-1/CTLA-4 immunotherapy resistance

Author

Rodriguez, B. Leticia, primary, Chen, Limo, additional, Li, Yanli, additional, Miao, Shucheng, additional, Peng, David H., additional, Fradette, Jared J., additional, Diao, Lixia, additional, Konen, Jessica M., additional, Alvarez, Frank R. Rojas, additional, Solis, Luisa M., additional, Yi, Xiaohui, additional, Padhye, Aparna, additional, Gibson, Laura A., additional, Ochieng, Joshua K., additional, Zhou, Xiaofei, additional, Wang, Jing, additional, and Gibbons, Don L., additional

Published
2023
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47. Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: A Single Center Experience

Author

Altan, Mehmet, primary, Soto, Felipe, additional, Zhong, Linda L, additional, Akhmedzhanov, Fechukwu O, additional, Wilson, Nathaniel R, additional, Zarifa, Abdulrazzak, additional, Albittar, Aya A, additional, Yang, Vincent, additional, Lewis, Jeff, additional, Rinsurongkawong, Waree, additional, Jack Lee, J, additional, Rinsurongkawong, Vadeerat, additional, Zhang, Jianjun, additional, Gibbons, Don L, additional, Vaporciyan, Ara A, additional, Jennings, Kristofer, additional, Khawaja, Fareed, additional, Faiz, Saadia A, additional, Shannon, Vickie R, additional, Shroff, Girish, additional, Godoy, Myrna C B, additional, Daver, Naval G, additional, Gandhi, Saumil, additional, Mendoza, Tito R, additional, Naing, Aung, additional, Daniel-MacDougall, Carrie, additional, Heymach, John V, additional, and Sheshadri, Ajay, additional

Published
2023
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48. Comprehensive T cell repertoire characterization of non-small cell lung cancer

Author

Reuben, Alexandre, Zhang, Jiexin, Chiou, Shin-Heng, Gittelman, Rachel M., Li, Jun, Lee, Won-Chul, Fujimoto, Junya, Behrens, Carmen, Liu, Xiaoke, Wang, Feng, Quek, Kelly, Wang, Chunlin, Kheradmand, Farrah, Chen, Runzhe, Chow, Chi-Wan, Lin, Heather, Bernatchez, Chantale, Jalali, Ali, Hu, Xin, Wu, Chang-Jiun, Eterovic, Agda Karina, Parra, Edwin Roger, Yusko, Erik, Emerson, Ryan, Benzeno, Sharon, Vignali, Marissa, Wu, Xifeng, Ye, Yuanqing, Little, Latasha D., Gumbs, Curtis, Mao, Xizeng, Song, Xingzhi, Tippen, Samantha, Thornton, Rebecca L., Cascone, Tina, Snyder, Alexandra, Wargo, Jennifer A., Herbst, Roy, Swisher, Stephen, Kadara, Humam, Moran, Cesar, Kalhor, Neda, Zhang, Jianhua, Scheet, Paul, Vaporciyan, Ara A., Sepesi, Boris, Gibbons, Don L., Robins, Harlan, Hwu, Patrick, Heymach, John V., Sharma, Padmanee, Allison, James P., Baladandayuthapani, Veera, Lee, Jack J., Davis, Mark M., Wistuba, Ignacio I., Futreal, P. Andrew, and Zhang, Jianjun

Published
2020
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49. ZEB1/NuRD complex suppresses TBC1D2b to stimulate E-cadherin internalization and promote metastasis in lung cancer

Author

Manshouri, Roxsan, Coyaud, Etienne, Kundu, Samrat T., Peng, David H., Stratton, Sabrina A., Alton, Kendra, Bajaj, Rakhee, Fradette, Jared J., Minelli, Rosalba, Peoples, Michael D., Carugo, Alessandro, Chen, Fengju, Bristow, Christopher, Kovacs, Jeffrey J., Barton, Michelle C., Heffernan, Tim, Creighton, Chad J., Raught, Brian, and Gibbons, Don L.

Published
2019
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50. The epithelial-to-mesenchymal transition activator ZEB1 initiates a prometastatic competing endogenous RNA network

Author

Tan, Xiaochao, Banerjee, Priyam, Liu, Xin, Yu, Jiang, Gibbons, Don L., Wu, Ping, Scott, Kenneth L., Diao, Lixia, Zheng, Xiaofeng, Wang, Jing, Jalali, Ali, Suraokar, Milind, Fujimoto, Junya, Behrens, Carmen, Liu, Xiuping, Liu, Chang-gong, Creighton, Chad J., Wistuba, Ignacio I., and Kurie, Jonathan M.

Subjects
Lung cancer -- Development and progression -- Prognosis, MicroRNA -- Health aspects -- Physiological aspects, Cancer metastasis -- Genetic aspects -- Development and progression, Transcription factors -- Health aspects, Health care industry
Abstract

Epithelial tumor cells undergo epithelial-to-mesenchymal transition (EMT) to gain metastatic activity. Competing endogenous RNAs (ceRNAs) have binding sites for a common set of microRNAs (miRs) and regulate each other's expression by sponging miRs. Here, we address whether ceRNAs govern metastasis driven by the EMT- activating transcription factor ZEB1. High miR-181b levels were correlated with an improved prognosis in human lung adenocarcinomas, and metastatic tumor cell lines derived from a murine lung adenocarcinoma model in which metastasis is ZEB1- driven were enriched in miR-181b targets. ZEB1 relieved a strong basal repression of [[alpha].sub.1] integrin (ITGA1) mRNA, which in turn upregulated adenylyl cyclase 9 mRNA (ADCY9) by sponging miR181b. Ectopic expression of the ITGA1 3'-untranslated region reversed miR-181b-mediated metastasis suppression and increased the levels of adenylyl cyclase 9 protein (AC9), which promoted tumor cell migration and metastasis. In human lung adenocarcinomas, ITGA1 and ADCY9 levels were positively correlated, and an AC9-activated transcriptomic signature had poor-prognostic value. Thus, ZEB1 initiates a miR-181b-regulated ceRNA network to drive metastasis., Introduction Metastasis is the primary cause of cancer-related death (1) and is driven by tumor cells that are uniquely capable of switching reversibly between epithelial and mesenchymal states in response [...]

Published
2018
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