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51. Spatial Immunoprofiling of Adenoid Cystic Carcinoma Reveals B7-H4 Is a Therapeutic Target for Aggressive Tumors

Author

Sousa, Luana Guimaraes, primary, McGrail, Daniel J., additional, Lazar Neto, Felippe, additional, Li, Kaiyi, additional, Marques-Piubelli, Mario L., additional, Ferri-Borgogno, Sammy, additional, Dai, Hui, additional, Mitani, Yoshitsugu, additional, Spardy Burr, Nicole, additional, Cooper, Zachary A., additional, Kinneer, Krista, additional, Cortez, Maria Angelica, additional, Lin, Shiaw-Yih, additional, Bell, Diana, additional, El Naggar, Adel, additional, Burks, Jared, additional, and Ferrarotto, Renata, additional

Published
2023
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52. Phase II Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma

Author

Ferrarotto, Renata, primary, Sousa, Luana G., additional, Feng, Lei, additional, Mott, Frank, additional, Blumenschein, George, additional, Altan, Mehmet, additional, Bell, Diana, additional, Bonini, Flavia, additional, Li, Kaiyi, additional, Marques-Piubelli, Mario L., additional, Dal Lago, Eduardo A., additional, Johnson, Jason J., additional, Mitani, Yoshitsugu, additional, Godoy, Myrna, additional, Lee, Anna, additional, Kupferman, Michael, additional, Hanna, Ehab, additional, Glisson, Bonnie S., additional, Elamin, Yasir, additional, and El-Naggar, Adel, additional

Published
2023
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53. Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune‐related adverse event reveal upregulation of toll‐like receptor 4/complement‐induced innate immune response and increased density ofT H 1T‐cells

Author

Marques‐Piubelli, Mario L., primary, Seervai, Riyad N. H., additional, Mudaliar, Kumaran M., additional, Ma, Wencai, additional, Milton, Denái R., additional, Wang, Jing, additional, Muhlbauer, Aaron, additional, Parra, Edwin R., additional, Solis, Luisa M., additional, Nagarajan, Priyadharsini, additional, Speiser, Jodi, additional, Hudgens, Courtney, additional, Cho, Woo Cheal, additional, Aung, Phyu P., additional, Patel, Anisha, additional, Pacha, Omar, additional, Nelson, Kelly C., additional, Tetzlaff, Michael T., additional, Amaria, Rodabe N., additional, Torres‐Cabala, Carlos A., additional, Prieto, Victor G., additional, Wistuba, Ignacio I., additional, and Curry, Jonathan L., additional

Published
2023
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55. Data from Follicular Lymphoma Microenvironment Characteristics Associated with Tumor Cell Mutations and MHC Class II Expression

Author

Han, Guangchun, primary, Deng, Qing, primary, Marques-Piubelli, Mario L., primary, Dai, Enyu, primary, Dang, Minghao, primary, Ma, Man Chun John, primary, Li, Xubin, primary, Yang, Haopeng, primary, Henderson, Jared, primary, Kudryashova, Olga, primary, Meerson, Mark, primary, Isaev, Sergey, primary, Kotlov, Nikita, primary, Nomie, Krystle J., primary, Bagaev, Alexander, primary, Parra, Edwin R., primary, Solis Soto, Luisa M., primary, Parmar, Simrit, primary, Hagemeister, Fredrick B., primary, Ahmed, Sairah, primary, Iyer, Swaminathan P., primary, Samaniego, Felipe, primary, Steiner, Raphael, primary, Fayad, Luis, primary, Lee, Hun, primary, Fowler, Nathan H., primary, Flowers, Christopher R., primary, Strati, Paolo, primary, Westin, Jason R., primary, Neelapu, Sattva S., primary, Nastoupil, Loretta J., primary, Vega, Francisco, primary, Wang, Linghua, primary, and Green, Michael R., primary

Published
2023
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56. Supplementary Data from Follicular Lymphoma Microenvironment Characteristics Associated with Tumor Cell Mutations and MHC Class II Expression

Author

Han, Guangchun, primary, Deng, Qing, primary, Marques-Piubelli, Mario L., primary, Dai, Enyu, primary, Dang, Minghao, primary, Ma, Man Chun John, primary, Li, Xubin, primary, Yang, Haopeng, primary, Henderson, Jared, primary, Kudryashova, Olga, primary, Meerson, Mark, primary, Isaev, Sergey, primary, Kotlov, Nikita, primary, Nomie, Krystle J., primary, Bagaev, Alexander, primary, Parra, Edwin R., primary, Solis Soto, Luisa M., primary, Parmar, Simrit, primary, Hagemeister, Fredrick B., primary, Ahmed, Sairah, primary, Iyer, Swaminathan P., primary, Samaniego, Felipe, primary, Steiner, Raphael, primary, Fayad, Luis, primary, Lee, Hun, primary, Fowler, Nathan H., primary, Flowers, Christopher R., primary, Strati, Paolo, primary, Westin, Jason R., primary, Neelapu, Sattva S., primary, Nastoupil, Loretta J., primary, Vega, Francisco, primary, Wang, Linghua, primary, and Green, Michael R., primary

Published
2023
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57. Supplementary Figure from Follicular Lymphoma Microenvironment Characteristics Associated with Tumor Cell Mutations and MHC Class II Expression

Author

Han, Guangchun, primary, Deng, Qing, primary, Marques-Piubelli, Mario L., primary, Dai, Enyu, primary, Dang, Minghao, primary, Ma, Man Chun John, primary, Li, Xubin, primary, Yang, Haopeng, primary, Henderson, Jared, primary, Kudryashova, Olga, primary, Meerson, Mark, primary, Isaev, Sergey, primary, Kotlov, Nikita, primary, Nomie, Krystle J., primary, Bagaev, Alexander, primary, Parra, Edwin R., primary, Solis Soto, Luisa M., primary, Parmar, Simrit, primary, Hagemeister, Fredrick B., primary, Ahmed, Sairah, primary, Iyer, Swaminathan P., primary, Samaniego, Felipe, primary, Steiner, Raphael, primary, Fayad, Luis, primary, Lee, Hun, primary, Fowler, Nathan H., primary, Flowers, Christopher R., primary, Strati, Paolo, primary, Westin, Jason R., primary, Neelapu, Sattva S., primary, Nastoupil, Loretta J., primary, Vega, Francisco, primary, Wang, Linghua, primary, and Green, Michael R., primary

Published
2023
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59. Additional file 1 of PD-L1+ macrophages are associated with favorable features in primary mediastinal (thymic) large B-cell lymphoma

Author

Steiner, Raphael E., Parra, Edwin R., Vega, Francisco, Feng, Lei, Westin, Jason R., Neelapu, Sattva S., Strati, Paolo, Green, Michael R., Flowers, Christopher R., Solis, Luisa M., Wistuba, Ignacio I., Ahmed, Sairah, Nair, Ranjit, Hagemeister, Fredrick B., Noorani, Mansoor, and Marques-Piubelli, Mario L.

Abstract

Additional file 1: Methods; Figure S1. Representative pictures showing different cell densities of CD30+PD-L1+ cells. A-C) Multiplex immunofluorescence image of a case with low cell density of CD30+, PD-L1+, and CD30+PD-L1+ cells median: 20.46 cells/mm2, respectively. D-E) Multiplex immunofluorescence image of a case with high cell density of CD30+, PD-L1+, and CD30+PD-L1+ cells (median: 604.62 cells/mm2), respectively. Supplementary Table 1.

Published
2023
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60. CD30 expression is frequently decreased in relapsed classic Hodgkin lymphoma after anti‐CD30 CAR T‐cell therapy.

Author

Marques‐Piubelli, Mario L., Kim, Do Hwan, Medeiros, L. Jeffrey, Lu, Wei, Khan, Khaja, Gomez‐Bolanos, Lorena Isabel, Rodriguez, Saxon, Parra, Edwin R., Ok, Chi Young, Aradhya, Akanksha, Solis, Luisa M, Nieto, Yago L., Steiner, Raphael, Ahmed, Sairah, and Vega, Francisco

Subjects
*CD30 antigen, *HODGKIN'S disease, *T cells, *CHIMERIC antigen receptors, *GENE amplification
Abstract

Chimeric antigen receptor (CAR) T‐cells anti‐CD30 is an innovative therapeutic option that has been used to treat cases of refractory/relapsed (R/R) classic Hodgkin lymphoma (CHL). Limited data are available regarding the CD30 expression status of patients who relapsed after this therapy. This is the first study to show decreased CD30 expression in R/R CHL in patients (n = 5) who underwent CAR T‐cell therapy in our institution between 2018 and 2022. Although conventional immunohistochemical assays showed decreased CD30 expression in neoplastic cells in all cases (8/8) the tyramide amplification assay and RNAScope in situ hybridisation detected CD30 expression at different levels in 100% (n = 8/8) and 75% (n = 3/4), respectively. Hence, our findings document that certain levels of CD30 expression are retained by the neoplastic cells. This is not only of biological interest but also diagnostically important, as detection of CD30 is an essential factor in establishing a diagnosis of CHL. [ABSTRACT FROM AUTHOR]

Published
2023
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61. Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune‐related adverse event reveal upregulation of toll‐like receptor 4/complement‐induced innate immune response and increased density of TH1 T‐cells

Author

Marques‐Piubelli, Mario L., Seervai, Riyad N. H., Mudaliar, Kumaran M., Ma, Wencai, Milton, Denái R., Wang, Jing, Muhlbauer, Aaron, Parra, Edwin R., Solis, Luisa M., Nagarajan, Priyadharsini, Speiser, Jodi, Hudgens, Courtney, Cho, Woo Cheal, Aung, Phyu P., Patel, Anisha, Pacha, Omar, Nelson, Kelly C., Tetzlaff, Michael T., Amaria, Rodabe N., and Torres‐Cabala, Carlos A.

Subjects
*DRUG side effects, *GENE expression profiling, *B cells, *BULLOUS pemphigoid, *IMMUNE response, *TOLL-like receptors, *T cells
Abstract

Background: Immune checkpoint inhibitor (ICI)‐based cancer therapies cause a variety of cutaneous immune‐related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP‐irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. Methods: BP‐irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T‐cells (CD3 and CD8), T helper 1 (TH1) cells (Tbet), TH2 cells (Gata3), TH17 cells (RORγT), and regulatory T‐cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. Results: Compared with de novo BP controls, BP‐irAE samples exhibited upregulation of 30 mRNA transcripts (p < 0.025), including toll‐like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p < 0.025), including genes associated with TH2, TH17, and B‐cell immune response. BP‐irAE demonstrated a greater density of Tbet+ (TH1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. Conclusions: BP‐irAE exhibited activation of the TLR4/complement‐driven classical innate immune response pathway, with dermal TH1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP‐irAE. [ABSTRACT FROM AUTHOR]

Published
2023
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62. CD19 CAR-T Outcomes in Patients with EBV-Positive DLBCL

Author

Nair, Ranjit, primary, Ayers, Amy, additional, Nastoupil, Loretta J., additional, Gunther, Jillian R., additional, Fayad, Luis, additional, Fowler, Nathan H., additional, Miranda, Roberto N., additional, Hagemeister, Fredrick B., additional, Lee, Hun Ju, additional, Rodriguez, Maria Alma, additional, Steiner, Raphael, additional, Strati, Paolo, additional, Nieto, Yago, additional, Ramdial, Jeremy L., additional, Chihara, Dai, additional, Wang, Michael L., additional, Malpica Castillo, Luis E, additional, Saini, Neeraj, additional, Jain, Preetesh, additional, Pinnix, Chelsea C., additional, Dabaja, Bouthaina S., additional, Green, Michael R, additional, Flowers, Christopher R., additional, Medeiros, L. Jeffrey, additional, Marques-Piubelli, Mario L., additional, Vega, Francisco, additional, Noorani, Mansoor, additional, Ahmed, Sairah, additional, Westin, Jason, additional, Neelapu, Sattva S., additional, Feng, Lei, additional, and Iyer, Swaminathan Padmanabhan, additional

Published
2022
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64. EOMES+ Tr1-like Cells Are Enriched in Areas of NLPHL Group II (Patterns D to F) Supporting the Role of Tregs in Disease Recurrence/Progression

Author

Marques-Piubelli, Mario L., primary, Dueñas, Daniela, additional, Qiu, Lianqun, additional, Nahmod, Karen, additional, Cho, Jeong Hee, additional, Jiang, Mei, additional, McAllen, Salome, additional, Solis Soto, Luisa M, additional, Steiner, Raphael, additional, Pinnix, Chelsea C., additional, Wistuba, Ignacio I., additional, Parra, Edwin R., additional, and Vega, Francisco, additional

Published
2022
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67. Follicular Lymphoma Microenvironment Characteristics Associated with Tumor Cell Mutations and MHC Class II Expression

Author

Han, Guangchun, primary, Deng, Qing, additional, Marques-Piubelli, Mario L., additional, Dai, Enyu, additional, Dang, Minghao, additional, Ma, Man Chun John, additional, Li, Xubin, additional, Yang, Haopeng, additional, Henderson, Jared, additional, Kudryashova, Olga, additional, Meerson, Mark, additional, Isaev, Sergey, additional, Kotlov, Nikita, additional, Nomie, Krystle J., additional, Bagaev, Alexander, additional, Parra, Edwin R., additional, Solis Soto, Luisa M., additional, Parmar, Simrit, additional, Hagemeister, Fredrick B., additional, Ahmed, Sairah, additional, Iyer, Swaminathan P., additional, Samaniego, Felipe, additional, Steiner, Raphael, additional, Fayad, Luis, additional, Lee, Hun, additional, Fowler, Nathan H., additional, Flowers, Christopher R., additional, Strati, Paolo, additional, Westin, Jason R., additional, Neelapu, Sattva S., additional, Nastoupil, Loretta J., additional, Vega, Francisco, additional, Wang, Linghua, additional, and Green, Michael R., additional

Published
2022
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68. Multiomics profiling and association with molecular and immune features in association with benefits from immunotherapy for patients with previously treated stage IV or recurrent squamous cell lung cancer from the phase III SWOG LungMAP S1400I trial.

Author

Parra, Edwin R., primary, Duose, Dzifa Yawa, additional, Zhang, Jiexin, additional, Redman, Mary Weber, additional, Lazcano Segura, Rossana, additional, Marques-Piubelli, Mario L., additional, Laberiano Fernandez, Caddie, additional, Zhang, BaiLi, additional, Lindsay, James, additional, Moravec, Radim, additional, Kannan, Kasthuri, additional, Luthra, Rajyalakshmi, additional, Alatrash, Gheath, additional, Herbst, Roy S., additional, Wistuba, Ignacio Ivan, additional, Gettinger, Scott N., additional, Bazhenova, Lyudmila, additional, Lee, J. Jack, additional, Zhang, Jianjun, additional, and Haymaker, Cara L., additional

Published
2022
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69. Single-cell immune mapping of adenoid cystic carcinoma (ACC) reveals potential therapeutic targets for the aggressive solid subtype.

Author

Guimaraes de Sousa, Luana, primary, Lazar Neto, Felippe, additional, McGrail, Daniel James, additional, Li, Kaiyi, additional, Marques-Piubelli, Mario L., additional, Ferri Borgogno, Sammy, additional, Dai, Hui, additional, Mitani, Yoshitsugu, additional, Lin, Shiaw-Yih, additional, El-Naggar, Adel K., additional, Bell, Diana, additional, Burks, Jared, additional, and Ferrarotto, Renata, additional

Published
2022
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71. CD70 is a Potential Target Biomarker in Peripheral T‐cell Lymphomas

Author

Marques‐Piubelli, Mario L., primary, Sagert, Jason, additional, Pham, Minh Thu, additional, Will, Matthias, additional, Henderson, Dan, additional, Tipton, Kimberly, additional, Iyer, Swaminathan, additional, Lu, Wei, additional, Khan, Khaja B., additional, Hamana, Leticia, additional, Chapman, Jennifer R., additional, Thakral, Beenu, additional, Xu, Jie, additional, Miranda, Roberto N., additional, Jennings, Kristofer, additional, Solis, Luisa M., additional, and Vega, Francisco, additional

Published
2022
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72. PD-L1+ macrophages are associated with favorable features in primary mediastinal (thymic) large B-cell lymphoma.

Author

Steiner, Raphael E., Parra, Edwin R., Vega, Francisco, Feng, Lei, Westin, Jason R., Neelapu, Sattva S., Strati, Paolo, Green, Michael R., Flowers, Christopher R., Solis, Luisa M., Wistuba, Ignacio I., Ahmed, Sairah, Nair, Ranjit, Hagemeister, Fredrick B., Noorani, Mansoor, and Marques-Piubelli, Mario L.

Subjects
MACROPHAGES, PROGNOSIS, THYMUS tumors, NON-Hodgkin's lymphoma, LYMPHOMAS, DISEASE relapse
Abstract

Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a rare, aggressive subtype of non-Hodgkin lymphoma and has a complex inflammatory microenvironment. Although most patients can be cured with standard-of-care immunochemotherapy, patients who have disease relapse have an unfavorable prognosis. Pre-treatment prognostic biomarkers in PMBCL are needed. In this retrospective study, we analyzed the clinical features and outcomes of PMBCL patients and their association with immune cell subpopulations identified by multiplex immunofluorescence at initial diagnosis. Two different antibody panels were used to assess macrophages in tissue biopsy specimens collected before the initiation of induction therapy. Twelve PMBCL patients, including five patients who had disease relapse, were included in the analysis. At a median follow-up time of 32.2 months, the median progression-free and overall survival durations were not reached. Our findings suggest that a high density of PD-L1+ macrophages is associated with favorable features, such as early disease stage and the absence of B-symptoms, and indicate that a high percentage of PD-L1+ macrophages and high densities of CD30+PD-L1+ cells and CD30+ cells might be associated with a lower risk of relapse within 12 months of therapy initiation. Further studies are needed to develop a biomarker signature predictive of treatment response with therapeutic consequences for patients with newly diagnosed PMBCL. [ABSTRACT FROM AUTHOR]

Published
2023
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73. Spontaneous tumor regression following COVID-19 vaccination

Author

Sousa, Luana Guimaraes de, primary, McGrail, Daniel J, additional, Li, Kaiyi, additional, Marques-Piubelli, Mario L, additional, Gonzalez, Cipriano, additional, Dai, Hui, additional, Ferri-Borgogno, Sammy, additional, Godoy, Myrna, additional, Burks, Jared, additional, Lin, Shiaw-Yih, additional, Bell, Diana, additional, and Ferrarotto, Renata, additional

Published
2022
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74. CD70 Expression in Mature T-Cell Lymphomas

Author

Marques-Piubelli, Mario L., primary, Solis Soto, Luisa, additional, Iyer, Swaminathan Padmanabhan, additional, Sagert, Jason, additional, Pham, Minh Thu, additional, Tipton, Kimberly, additional, Lu, Wei, additional, Khan, Khaja B, additional, Hamana Zorrilla, Leticia G, additional, Chapman, Jennifer R, additional, Thakral, Beenu, additional, Xu, Jie, additional, Miranda, Roberto N., additional, Jennings, Kristofer, additional, and Vega, Francisco, additional

Published
2021
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75. Sirpα and CSF1R Positive Tissue Macrophages Are Increased in Patients with Follicular Lymphoma Who Relapse after Frontline Lenalidomide and Rituximab

Author

Marques-Piubelli, Mario L., primary, Parra, Edwin R., additional, Feng, Lei, additional, Gallardo, Mariana, additional, Solis Soto, Luisa, additional, Wistuba, Ignacio I., additional, Flowers, Christopher R., additional, Neelapu, Sattva S., additional, Vega, Francisco, additional, and Strati, Paolo, additional

Published
2021
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76. Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

Author

Seervai, Riyad N. H., primary, Cho, Woo Cheal, additional, Chu, Emily Y., additional, Marques‐Piubelli, Mario L., additional, Ledesma, Debora A., additional, Richards, Kristen, additional, Heberton, Meghan M., additional, Nelson, Kelly C., additional, Nagarajan, Priyadharsini, additional, Torres‐Cabala, Carlos A., additional, Prieto, Victor G., additional, and Curry, Jonathan L., additional

Published
2021
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77. Extranodal NK/T-cell lymphoma, nasal type presenting as primary intestinal lymphoma vs intestinal T-cell lymphoma: A borderline diagnostic category in the revised WHO classification

Author

Beltrán, Brady E., primary, Marques-Piubelli, Mario L., additional, Quiñones, M. Pilar, additional, Cotrina, Esther, additional, Palomino, Eugenio A., additional, Morales, Johnny, additional, Ramos, Wilder, additional, Sotomayor, Eduardo M., additional, Chavez, Julio C., additional, Castillo, Jorge J., additional, and Miranda, Roberto N., additional

Published
2021
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78. Extranodal NK/T-cell lymphoma, nasal type with extensive cardiopulmonary involvement

Author

Marques-Piubelli, Mario L., Sales, Gabriel Teixeira Montezuma, Clemente, Letícia Campos, Rosa, Lidiane Inês, Savioli, Mariana Lorenzi, Alvim, Ricardo Pires, Moreira, Raquel Megale, Frassetto, Fernando Pereira, Nascimento, Ellen Caroline Toledo do, and Siqueira, Sheila Aparecida Coelho

Subjects
Lymphoma, Extranodal NK-T-Cell, Epstein-Barr Virus Infections, Lymphoma, hemic and lymphatic diseases, Lymphoma, Non-Hodgkin
Abstract

Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT) is a rare type of Non-Hodgkin’s lymphoma, which usually presents with extranodal involvement and affects the nasal/upper aerodigestive tract in the classical presentation. Herein, we report the case of a 31-year-old, previously healthy, male patient diagnosed with ENKTL-NT with the involvement of the lung parenchyma and heart. Unfortunately, due to the rapid disease progression, the diagnosis was performed only at the autopsy. The authors highlight the rare clinical presentation of this type of lymphoma, as well as the challenging anatomopathological diagnosis in necrotic samples.

Published
2021

79. PARP and CDK4/6 Inhibitor Combination Therapy Induces Apoptosis and Suppresses Neuroendocrine Differentiation in Prostate Cancer

Author

Wu, Cheng, primary, Peng, Shan, additional, Pilié, Patrick G., additional, Geng, Chuandong, additional, Park, Sanghee, additional, Manyam, Ganiraju C., additional, Lu, Yungang, additional, Yang, Guang, additional, Tang, Zhe, additional, Kondraganti, Shakuntala, additional, Wang, Daoqi, additional, Hudgens, Courtney W., additional, Ledesma, Debora A., additional, Marques-Piubelli, Mario L., additional, Torres-Cabala, Carlos A., additional, Curry, Jonathan L., additional, Troncoso, Patricia, additional, Corn, Paul G., additional, Broom, Bradley M., additional, and Thompson, Timothy C., additional

Published
2021
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83. Case Report: Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Case Series on the Clinical and Histopathologic Spectrum of Adverse Cutaneous Reactions From Fatal Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis to Dermal Hypersensitivity Reaction

Author

Viscuse, Paul V., primary, Marques-Piubelli, Mario L., additional, Heberton, Meghan M., additional, Parra, Edwin Roger, additional, Shah, Amishi Y., additional, Siefker-Radtke, Arlene, additional, Gao, Jianjun, additional, Goswami, Sangeeta, additional, Ivan, Doina, additional, Curry, Jonathan L., additional, and Campbell, Matthew T., additional

Published
2021
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85. Ovarian mucinous neoplasms, intestinal type, in premenopausal patients, develop in abnormal ovaries

Author

Silva, Elvio, primary, Malpica, Anais, additional, Roma, Andres, additional, Ramalingam, Preetha, additional, Kim, Grace, additional, Bakkar, Rania, additional, Loghavi, Sanam, additional, Kim, Stacey, additional, Shaye-Brown, Alexandra, additional, Marques-Piubelli, Mario L., additional, Chisholm, Gary, additional, Gershenson, David M., additional, and Alvarado-Cabrero, Isabel, additional

Published
2021
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86. Extranodal NK/T-cell lymphoma, nasal type with extensive cardiopulmonary involvement

Author

Marques-Piubelli, Mario L., primary, Sales, Gabriel Teixeira Montezuma, additional, Clemente, Letícia Campos, additional, Savioli, Lidiane Inês Rosa Mariana Lorenzi, additional, Alvim, Ricardo Pires, additional, Moreira, Raquel Megale, additional, Frassetto, Fernando Pereira, additional, Nascimento, Ellen Caroline Toledo do, additional, and Siqueira, Sheila Aparecida Coelho, additional

Published
2021
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87. Expression of BCL2 alternative proteins and association with outcome in CLL patients treated with venetoclax

Author

Marques-Piubelli, Mario L., primary, Schlette, Ellen J., additional, Khoury, Joseph D., additional, Furqan, Fateeha, additional, Vega, Francisco, additional, Soto, Luisa M. Solis, additional, Wistuba, Ignacio I., additional, Wierda, William G., additional, Konopleva, Marina, additional, Ferrajoli, Alessandra, additional, and Strati, Paolo, additional

Published
2020
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89. Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy.

Author

Seervai, Riyad N. H., Cho, Woo Cheal, Chu, Emily Y., Marques‐Piubelli, Mario L., Ledesma, Debora A., Richards, Kristen, Heberton, Meghan M., Nelson, Kelly C., Nagarajan, Priyadharsini, Torres‐Cabala, Carlos A., Prieto, Victor G., and Curry, Jonathan L.

Subjects
CANCER treatment, MITOGEN-activated protein kinases, CELLULAR signal transduction, MYELOPROLIFERATIVE neoplasms, MOLECULAR genetics
Abstract

Background: Advances in molecular biology and genetics have contributed to breakthrough treatments directed at specific pathways associated with the development of cancer. Small‐molecule inhibitors (Nibs) aimed at a variety of cellular pathways have been efficacious; however, they are associated with significant dermatologic toxicities. Methods: We conducted a comprehensive review of dermatologic toxicities associated with Nibs categorized into the following five groups: (a) mitogen‐activated protein kinase; (b) growth factor/multi‐tyrosine kinase; (c) cell division/DNA repair; (d) signaling associated with myeloproliferative neoplasms; and (e) other signaling pathways. Prospective phase I, II, or III clinical trials, retrospective literature reviews, systematic reviews/meta‐analyses, and case reviews/reports were included for analysis. Results: Dermatologic toxicities reviewed were associated with every class of Nibs and ranged from mild to severe or life‐threatening adverse skin reactions. Inflammatory reactions manifesting as maculopapular, papulopustular/acneiform, and eczematous lesions were frequent types of dermatologic toxicities seen with Nibs. Squamous cell carcinoma with keratoacanthoma‐like features was associated with a subset of Nibs. Substantial overlap in dermatologic toxicities was found between Nibs. Conclusions: Dermatologic toxicities from Nibs are diverse and may overlap between classes of Nibs. Recognition of the various types of toxicities from Nibs is critical for patient care in the era of "oncodermatology/dermatopathology." [ABSTRACT FROM AUTHOR]

Published
2022
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90. Malignant Mesothelioma of the Peritoneum in Women

Author

Malpica, Anais, primary, Euscher, Elizabeth D., additional, Marques-Piubelli, Mario L., additional, Ferrufino-Schmidt, Maria C., additional, Miranda, Roberto N., additional, Sams, Ralph, additional, Royal, Richard E., additional, Raghav, Kanwal P.S., additional, Fournier, Keith F., additional, and Ramalingam, Preetha, additional

Published
2020
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91. Hypertrophic lichenoid dermatitis immune‐related adverse event during combined immune checkpoint and exportin inhibitor therapy: A diagnostic pitfall for superficially invasive squamous cell carcinoma

Author

Marques‐Piubelli, Mario L., primary, Tetzlaff, Michael T., additional, Nagarajan, Priyadharsini, additional, Duke, Taylor C., additional, Glitza Oliva, Isabella C., additional, Ledesma, Debora A., additional, Aung, Phyu P., additional, Torres‐Cabala, Carlos A., additional, Wistuba, Ignacio I., additional, Prieto, Victor G., additional, Nelson, Kelly C., additional, and Curry, Jonathan L., additional

Published
2020
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93. SIRPα+macrophages are increased in patients with FL who progress or relapse after frontline lenalidomide and rituximab

Author

Marques-Piubelli, Mario L., Parra, Edwin R., Feng, Lei, Soto, Luisa Solis, Gallardo, Mariana, Gouni, Sushanth, Samaniego, Felipe, Noorani, Mansoor, Hagemeister, Fredrick B., Westin, Jason R., Lee, Hun Ju, Rodriguez, Maria A., Neelapu, Sattva S., Gunther, Jillian R., Fowler, Nathan H., Flowers, Christopher R., Wistuba, Ignacio I., Nastoupil, Loretta J., Vega, Francisco, and Strati, Paolo

Abstract

Limited data exist regarding the outcome of patients with follicular lymphoma (FL) who relapse or progress after frontline lenalidomide and rituximab (R2). Moreover, mechanisms of resistance to R2in FL remain unclear, with increased protumoral macrophages suspected as a major contributory culprit to this phenomenon. This retrospective study analyzed the outcome of patients with advanced-stage FL grade 1 to 3A who relapsed or progressed after frontline R2. A multiplex immunofluorescence macrophage panel, including CD47, CD14, CD68, CD115 (also known as colony-stimulating factor 1 receptor [CSF1R]), CD163, CD172a (also known as signal regulatory protein α [SIRPα]), and CD274 (also known as programmed cell death-ligand 1 [PDL1]), was used to stain tissue biopsy specimens collected before initiation of R2and at the time of progression. Among 156 patients with advanced-stage FL treated with frontline R2, 33 (21%) relapsed or progressed and required second-line therapy, after a median of 33 months (range, 1-122 months). Second-line therapy was chemoimmunotherapy in 16 (48%) patients and other therapy in 17 (52%). The overall response rate was 78%, and complete response rate was 72%. Median progression-free survival was significantly longer in patients who received chemoimmunotherapy compared with other therapy (99 vs 25 months; P= .004). Three macrophage populations were significantly increased in tissue samples collected at progression compared with before frontline treatment: CD68+CD115+(P= .02), CD68+CD115+CD172a+(P= .02), and CD68+CD163+CD172a+(P= .01). Chemoimmunotherapy is an effective treatment strategy for patients with FL who relapse after frontline R2. Therapies targeting specific macrophage populations may yield novel approaches for improving outcomes with frontline R2.

Published
2022
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94. Expression of BCL2 alternative proteins and association with outcome in CLL patients treated with venetoclax.

Author

Marques-Piubelli, Mario L., Schlette, Ellen J., Khoury, Joseph D., Furqan, Fateeha, Vega, Francisco, Soto, Luisa M. Solis, Wistuba, Ignacio I., Wierda, William G., Konopleva, Marina, Ferrajoli, Alessandra, and Strati, Paolo

Subjects
*FLUDARABINE, *CHRONIC lymphocytic leukemia, *BCL-2 proteins, *BONE marrow
Abstract

Venetoclax, a BCL-2 inhibitor, is highly effective for the treatment of patients with chronic lymphocytic leukemia (CLL) and dependence on alternative proteins may result in resistance to BCL-2 inhibition. Patients with CLL treated with venetoclax as monotherapy at MD Anderson Cancer Center between 05/2012 and 01/2016 were included and pretreatment bone marrow was analyzed by immunohistochemistry (IHC) for BCL-W, BCL-XL, BCL2-A1 and MCL-1. Twenty-seven patients were included. BCL-W + and BCL-2A1+ was found in 15% and 7% of the patients, respectively. Both BCL-XL and MCL-1 were negative in all samples. A higher CR and longer PFS rates were observed in patients with BCL-W+ (p =.60, p =.46), BCL-2A1+ (p =.60, p =.29), and either BCL-W + or BCL-2A1+ (p =.33, p =.20), though not statistically significant. Pretreatment IHC expression of BCL-2 alternative proteins does not predict response to venetoclax in CLL, but may be a surrogate for an indolent biology. Sensitive techniques are needed to explore anti-apoptotic pathways. [ABSTRACT FROM AUTHOR]

Published
2021
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96. Epstein–Barr virus-associated B-cell lymphoproliferative disorders and lymphomas: a review

Author

Marques-Piubelli, Mario L., Salas, Yessenia I., Pachas, Carlos, Becker-Hecker, Renato, Vega, Francisco, and Miranda, Roberto N.

Abstract

In this review, we focus on B-cell lymphoproliferative disorders (LPDs) and lymphomas associated with Epstein–Barr virus (EBV). In some of these diseases—such as EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified—virus detection is required for the diagnosis, while in others its detection is not necessary for diagnosis. EBV infection has three main latency patterns (types III, II, and I). Different latency patterns are found in different LPD types and are related to the host immune system status. For each of the LPDs/lymphomas, we discuss the clinical presentation, epidemiology, pathology, immunophenotype, and genetic or molecular basis. We provide data for a better understanding of the relationships among the discussed diseases and other information that can be useful in differential diagnosis. Not included in this review are classic Hodgkin lymphoma and some specific variants of DLBCL, as these entities are discussed in separate reviews in this issue.

Published
2024
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98. Targeting T-Cell Lymphoma Using CD70-Directed Cord Blood-Derived CAR-NK Cells

Author

Rafei, Hind, Basar, Rafet, Acharya, Sunil, Zhang, Patrick, Liu, Pinghua, Moseley, Sadie Mae, Li, Ping, Daher, May, Agarwal, Nitin, Marques-Piubelli, Mario L., Uprety, Nadima, Melo Garcia, Luciana, Shanley, Mayra, Banerjee, Pinaki, Li, Ye, Rosemore, Samuel Levi, Kumar, Bijender, Nunez Cortes, Ana K., Biederstädt, Alexander, Islam, Sanjida, Kaplan, Mecit, Hu, Bingqian, Manzar, Gohar, Lin, Paul, Marin, David, Champlin, Richard E., Vega, Francisco, Shpall, Elizabeth J., and Rezvani, Katayoun

Abstract

T-cell lymphomas (TCL) are a heterogenous group of non-Hodgkin lymphoma characterized by resistance to conventional therapies posing an urgent need for safe and effective therapies. CAR-NK cells have emerged as a promising “off-the-shelf” cancer immunotherapy and are especially attractive for the treatment of T-cell malignancies. This is especially the case given the challenge of targeting T cell malignancies with CAR T cells due to shared antigens across the therapeutic, normal and malignant T cells posing the risk of CAR T cell fratricide, T-cell aplasia, and contamination of the CAR T products with malignant T cells. We have developed an FDA-approved system for ex vivoNK cell expansion, which reliably generates clinically relevant doses of GMP-grade NK cells from a cord blood (CB) unit. We have used this platform to engineer NK cells to express a CAR targeting CD19 using GMP-grade retroviral vectors and demonstrated the safety and efficacy of this platform in the clinic. We now propose to expand this approach to target TCL. CD70, a surface ligand of CD27, is overexpressed in a variety of cancers, including TCL. Signaling mediated by CD70-CD27 is thought to induce proliferation of TCL cells via activation of the NF-κB pathway. Thus, CD70 is an attractive target for CAR NK-cell therapy against TCL. We analyzed the publicly available primary TCL dataset (GSE19069) including anaplastic large cell lymphoma (30 samples), angioimmunoblastic TCL (37 samples), peripheral TCL (PTCL; 50 samples), and adult T cell leukemia/lymphoma (13 samples) for CD70 expression. The majority of the samples expressed CD70 transcript with a variable level of expression ( Figure 1). Using flow cytometry, we screened a panel of TCL cell lines with diverse histologic, cytogenetic and molecular properties for the expression of CD70. We demonstrated positive CD70 expression on most of the TCL cell lines profiled encompassing anaplastic large cell lymphoma (ALK+: KAR299; ALK-: MAC2A; fusion gene NPM-ALK+: SU-DHL1 and SUP-M2), hepatosplenic gamma-delta TCL (DERL-7), Sezary syndrome (SS; H9 and HuT78), and PTCL NOS (OCI-LY12). The CD70 intensity was highest on MAC2A, HuT78, KAR299 and SUP-M2, intermediate to low on DERL-7 and H9, and negative on SU-DHL1 and OCI-LY12. We designed a novel retroviral vector targeting CD70 that: 1) encodes the CD70-targeting CAR gene based on the CD27 extracellular domain; 2) ectopically produces interleukin (IL)-15 to support NK cell proliferation; and 3) expresses the suicide gene inducible caspase 9 ( iC9) that can be pharmacologically activated to eliminate transduced cells in the event of toxicity. The construct will be referred to as CAR.70/IL-15. Non-transduced (NT) NK cells and NK cells transduced with a construct that leads to IL-15 production without a CAR (IL-15 NK cells) were used as controls. We demonstrated that CAR.70/IL-15 NK cells had a significantly enhanced cytotoxicity compared to NT- and IL-15 NK cells against the CD70+ cell lines while there was no difference in cytotoxicity between the NK cell conditions in the negative cell lines pointing to a CD70-targeted fashion of anti-TCL NK cell cytotoxicity. Moreover, CAR.70/IL-15 NK cells exhibited greater cytotoxicity against CD70+ cell lines in long-term cytotoxicity assays ( Figure 2). In a tumor rechallenge assay against KAR299 where fresh tumor cells were added every 3-4 days, CAR.70/IL-15 NK cells showed superior potency in continuous tumor control. In addition, CAR.70/IL-15 NK cells exhibited higher levels of degranulation (CD107a) and cytokine production (TNFα and INF-γ) when cocultured with CD70+ TCL cell lines, compared to NT and IL-15 NK cells. Furthermore, these CAR NK cells targeting CD70 outperformed CAR NK cells engineered to target CD19, which is an irrelevant target for TCL, further confirming the specific CD70-targeted activity of CAR.70/IL-15 NK cells. CyTOF immunophenotyping revealed that CAR.70/IL-15 NK cells are characterized by the increased expression of markers of cytotoxicity such as granzyme-b, perforin, TRAIL; and activating coreceptors/proliferation markers such as DNAM, CD25 and Ki67. Taken together, our findings validate CD70 as a promising target for TCL treatment using CAR NK cells. Our approach provides a solid foundation for the clinical translation of CD70-targeting CAR NK-cell therapy for patients with TCL.

Published
2023
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99. Addition of Acalabrutinib to Lenalidomide and Rituximab Induces High Complete Response Rates in Patients with Previously Untreated Follicular Lymphoma: Results of a Phase II Study

Author

Strati, Paolo, Feng, Lei, Westin, Jason, Nair, Ranjit, Fayad, Luis, Rodriguez, Maria Alma, Chihara, Dai, Malpica, Luis, Henderson, Jared, Gallardo, Mariana, Marques-Piubelli, Mario L., Turova, Polina, Zaitsev, Aleksandr, Wang, Iris, Flowers, Christopher R., Nastoupil, Loretta J., and Neelapu, Sattva S.

Abstract

Background. We previously reported pro-tumoral macrophages may be associated with resistance to lenalidomide and rituximab (R 2) treatment in follicular lymphoma (FL) ( Marques-Piubelli, Blood Adv 2022). As pre-clinical studies suggest that BTK inhibition can mitigate the crosstalk between monocyte/macrophages and FL B cells, we hypothesized that acalabrutinib, a specific BTK inhibitor, may synergize with R 2without increasing toxicity. In agreement with this, the combination of acalabrutinib and R 2(aR 2) was shown to be safe and effective in patients with relapsed FL ( Strati P et al, ASH 2022). Here, we investigated the safety and efficacy of aR 2in previously untreated FL patients and analyzed the biological effects of this combination on peripheral blood immune cells.

Published
2023
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100. A Phase II Study of Loncastuximab Tesirine As Consolidation Strategy in Patients with LBCL in PR at Day 30 after CAR T-Cell Therapy

Author

Al Zaki, Ajlan, Feng, Lei, Westin, Jason, Nair, Ranjit, Fayad, Luis, Watson, Grace, Adkins, Sherry, Shpall, Elizabeth J., Marques-Piubelli, Mario L., Henderson, Jared, Nastoupil, Loretta J., Flowers, Christopher R., Ahmed, Sairah, Neelapu, Sattva S., and Strati, Paolo

Abstract

Background and Significance. Approximately 30% of patients with large B-cell lymphoma (LBCL) treated with autologous anti-CD19 CAR T-cell therapy (CART) achieve a partial response (PR) on day 30 (D30) assessment. Of those, up to 30% may spontaneously convert to a complete response (CR) during subsequent re-staging. While up to 70% of patients with D30 PR eventually progress, reliable biomarkers that help identify patients at risk are not yet available, and the current standard approach is close monitoring. CD19 expression is retained in most tumors of patients who relapse or progress after CART. Potential reasons for resistance in these tumors include T-cell dysfunction and tumor intrinsic mechanisms that resist T-cell mediated killing. Therefore, targeting such tumors with agents that have an alternative mechanism of action is likely to improve outcomes. To this regard, loncastuximab tesirine (Lonca) is an anti-CD19 antibody conjugated to a cytotoxic pyrrolobenzodiazepine dimer approved by the FDA for LBCL patients who relapse after at least 2 lines of systemic therapy. In the phase 2 LOTIS-2 study, Lonca was associated with an overall response rate of 48% and a CR rate of 24%, and included patients previously treated with CART. Grade 3-4 adverse events were observed in less than one third of patients, and were mainly represented by myelosuppression, skin toxicity and isolated GGT elevation.

Published
2023
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