Search

Your search keyword '"Kupper, Thomas S"' showing total 890 results
Start Over Author "Kupper, Thomas S"
890 results on '"Kupper, Thomas S"'

201. Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth

Author

Kleffel, Sonja, primary, Posch, Christian, additional, Barthel, Steven R., additional, Mueller, Hansgeorg, additional, Schlapbach, Christoph, additional, Guenova, Emmanuella, additional, Elco, Christopher P., additional, Lee, Nayoung, additional, Juneja, Vikram R., additional, Zhan, Qian, additional, Lian, Christine G., additional, Thomi, Rahel, additional, Hoetzenecker, Wolfram, additional, Cozzio, Antonio, additional, Dummer, Reinhard, additional, Mihm, Martin C., additional, Flaherty, Keith T., additional, Frank, Markus H., additional, Murphy, George F., additional, Sharpe, Arlene H., additional, Kupper, Thomas S., additional, and Schatton, Tobias, additional

Published
2015
Full Text
View/download PDF

202. Mucin 1 is a potential therapeutic target in cutaneous T-cell lymphoma

Author

Jain, Salvia, primary, Stroopinsky, Dina, additional, Yin, Li, additional, Rosenblatt, Jacalyn, additional, Alam, Maroof, additional, Bhargava, Parul, additional, Clark, Rachael A., additional, Kupper, Thomas S., additional, Palmer, Kristen, additional, Coll, Maxwell D., additional, Rajabi, Hasan, additional, Pyzer, Athalia, additional, Bar-Natan, Michal, additional, Luptakova, Katarina, additional, Arnason, Jon, additional, Joyce, Robin, additional, Kufe, Donald, additional, and Avigan, David, additional

Published
2015
Full Text
View/download PDF

206. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

Author

Watanabe, Rei, primary, Gehad, Ahmed, additional, Yang, Chao, additional, Scott, Laura L., additional, Teague, Jessica E., additional, Schlapbach, Christoph, additional, Elco, Christopher P., additional, Huang, Victor, additional, Matos, Tiago R., additional, Kupper, Thomas S., additional, and Clark, Rachael A., additional

Published
2015
Full Text
View/download PDF

207. Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism.

Author

Pan, Youdong, Tian, Tian, Park, Chang Ook, Lofftus, Serena Y., Mei, Shenglin, Liu, Xing, Luo, Chi, O'Malley, John T., Gehad, Ahmed, Teague, Jessica E., Divito, Sherrie J., Fuhlbrigge, Robert, Puigserver, Pere, Krueger, James G., Hotamisligil, Gökhan S., Clark, Rachael A., and Kupper, Thomas S.

Abstract

Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8+ TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8+ TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes. In vitro, CD8+ TRM cells, but not CD8+ TCM cells, demonstrated increased mitochondrial oxidative metabolism in the presence of exogenous FFAs; this increase was not seen in Fabp4/Fabp5 double-knockout CD8+ TRM cells. The persistence of CD8+ TRM cells in the skin was strongly diminished by inhibition of mitochondrial FFA β-oxidation in vivo. Moreover, skin CD8+ TRM cells that lacked Fabp4/Fabp5 were less effective at protecting mice from cutaneous viral infection, and lung Fabp4/Fabp5 double-knockout CD8+ TRM cells generated by skin vaccinia virus (VACV) infection were less effective at protecting mice from a lethal pulmonary challenge with VACV. Consistent with the mouse data, increased FABP4 and FABP5 expression and enhanced extracellular FFA uptake were also demonstrated in human CD8+ TRM cells in normal and psoriatic skin. These results suggest that FABP4 and FABP5 have a critical role in the maintenance, longevity and function of CD8+ TRM cells, and suggest that CD8+ TRM cells use exogenous FFAs and their oxidative metabolism to persist in tissue and to mediate protective immunity. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

209. Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma

Author

Litvinov, Ivan V, Netchiporouk, Elena, Cordeiro, Brendan, Zargham, Hanieh, Pehr, Kevin, Gilbert, Martin, Zhou, Youwen, Moreau, Linda, Woetmann, Anders, Ødum, Niels, Kupper, Thomas S, Sasseville, Denis, Litvinov, Ivan V, Netchiporouk, Elena, Cordeiro, Brendan, Zargham, Hanieh, Pehr, Kevin, Gilbert, Martin, Zhou, Youwen, Moreau, Linda, Woetmann, Anders, Ødum, Niels, Kupper, Thomas S, and Sasseville, Denis

Abstract

Cutaneous T-cell lymphoma (CTCL) is a potentially devastating malignancy. The pathogenesis of this cancer remains poorly elucidated. Previous studies focused on analysis of expression and function of known oncogenes and tumor suppressor genes. However, emerging reports highlight that it is also important to analyze the expression of genes that are ectopically expressed in CTCL (e.g., embryonic stem cell genes (ESC), cancer testis (CT) genes, etc.). Currently, it is not known whether ESC genes are expressed in CTCL. In the current work, we analyze by RT-PCR the expression of 26 ESC genes, many of which are known to regulate pluripotency and promote cancer stem cell-like phenotype, in a historic cohort of 60 patients from Boston and in a panel of 11 patient-derived CTCL cell lines and compare such expression to benign inflammatory dermatoses that often clinically mimic CTCL. Our findings document that many critical ESC genes including NANOG, SOX2, OCT4 (POU5F1) and their upstream and downstream signaling members are expressed in CTCL. Similarly, polycomb repressive complex 2 (PRC2) genes (i.e., EZH2, EED, and SUZ12) are also expressed in CTCL lesional skin. Furthermore, select ESC genes (OCT4, EED, TCF3, THAP11, CHD7, TIP60, TRIM28) are preferentially expressed in CTCL samples when compared to benign skin biopsies. Our work suggests that ESC genes are ectopically expressed together with CT genes, thymocyte development genes and B cell-specific genes and may be working in concert to promote tumorigenesis. Specifically, while ESC genes may be promoting cancer stem cell-like phenotype, CT genes may be contributing to aneuploidy and genomic instability by producing aberrant chromosomal translocations. Further analysis of ESC expression and function in this cancer will greatly enhance our fundamental understanding of CTCL and will help us identify novel therapeutic targets.

Published
2014

210. Analysis of STAT4 expression in cutaneous T-cell lymphoma (CTCL) patients and patient-derived cell lines

Author

Litvinov, Ivan V, Cordeiro, Brendan, Fredholm, Simon Mayland, Ødum, Niels, Zargham, Hanieh, Huang, Yuanshen, Zhou, Youwen, Pehr, Kevin, Kupper, Thomas S, Woetmann, Anders, Sasseville, Denis, Litvinov, Ivan V, Cordeiro, Brendan, Fredholm, Simon Mayland, Ødum, Niels, Zargham, Hanieh, Huang, Yuanshen, Zhou, Youwen, Pehr, Kevin, Kupper, Thomas S, Woetmann, Anders, and Sasseville, Denis

Abstract

Deregulation of STAT signaling has been implicated in the pathogenesis for a variety of cancers, including CTCL. Recent reports indicate that loss of STAT4 expression is an important prognostic marker for CTCL progression and is associated with the acquisition of T helper 2 cell phenotype by malignant cells. However, little is known about the molecular mechanism behind the downregulation of STAT4 in this cancer. In the current work we test the expression of STAT4 and STAT6 via RT-PCR and/or Western Blot in CTCL lesional skin samples and in immortalized patient-derived cell lines. In these malignant cell lines we correlate the expression of STAT4 and STAT6 with the T helper (Th) phenotype markers and test the effect of Histone Deacetylase (HDAC) inhibitors and siRNA-mediated knock down of miR-155 on STAT4 expression. Our findings demonstrate that STAT4 expression correlates with Th1 phenotype, while STAT6 is associated with the Th2 phenotype. Our results further document that STAT4 and STAT6 genes are inversely regulated in CTCL. Treatment with HDAC inhibitors upregulates STAT4 expression, while at the same time decreases STAT6 expression in MyLa cells. Also, siRNA-mediated knock down of miR-155 leads to upregulation in STAT4 expression in MyLa cells. In summary, our results suggest that loss of STAT4 expression and associated switch to Th2 phenotype during Mycosis Fungoides progression may be driven via aberrant histone acetylation and/or upregulation of oncogenic miR-155 microRNA.

Published
2014

212. MUC1 As a Potential Therapeutic Target in Cutaneous T-Cell Lymphoma

Author

Jain, Salvia, primary, Alam, Maroof, additional, Rajabi, Hasan, additional, Stroopinsky, Dina, additional, Yin, Li, additional, Rosenblatt, Jacalyn, additional, Palmer, Kristen A, additional, Coll, Maxwell Douglas, additional, Pyzer, Athalia Rachel, additional, Luptakova, Katarina, additional, Arnason, Jon, additional, Joyce, Robin, additional, Bar-Natan, Michal, additional, Somaiya, Poorvi, additional, Clark, Rachael A, additional, Kupper, Thomas S., additional, Kufe, Donald, additional, and Avigan, David, additional

Published
2014
Full Text
View/download PDF

213. Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma

Author

Litvinov, Ivan V, primary, Netchiporouk, Elena, additional, Cordeiro, Brendan, additional, Zargham, Hanieh, additional, Pehr, Kevin, additional, Gilbert, Martin, additional, Zhou, Youwen, additional, Moreau, Linda, additional, Woetmann, Anders, additional, Ødum, Niels, additional, Kupper, Thomas S, additional, and Sasseville, Denis, additional

Published
2014
Full Text
View/download PDF

218. Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS–STING signalling

Author

Eaglesham, James B., Pan, Youdong, Kupper, Thomas S., and Kranzusch, Philip J.

Abstract

Cytosolic DNA triggers innate immune responses through the activation of cyclic GMP–AMP synthase (cGAS) and production of the cyclic dinucleotide second messenger 2′,3′-cyclic GMP–AMP (cGAMP)1–4. 2′,3′-cGAMP is a potent inducer of immune signalling; however, no intracellular nucleases are known to cleave 2′,3′-cGAMP and prevent the activation of the receptor stimulator of interferon genes (STING)5–7. Here we develop a biochemical screen to analyse 24 mammalian viruses, and identify poxvirus immune nucleases (poxins) as a family of 2′,3′-cGAMP-degrading enzymes. Poxins cleave 2′,3′-cGAMP to restrict STING-dependent signalling and deletion of the poxin gene (B2R) attenuates vaccinia virus replication in vivo. Crystal structures of vaccinia virus poxin in pre- and post-reactive states define the mechanism of selective 2′,3′-cGAMP degradation through metal-independent cleavage of the 3′–5′ bond, converting 2′,3′-cGAMP into linear Gp[2′–5′]Ap[3′]. Poxins are conserved in mammalian poxviruses. In addition, we identify functional poxin homologues in the genomes of moths and butterflies and the baculoviruses that infect these insects. Baculovirus and insect host poxin homologues retain selective 2′,3′-cGAMP degradation activity, suggesting an ancient role for poxins in cGAS–STING regulation. Our results define poxins as a family of 2′,3′-cGAMP-specific nucleases and demonstrate a mechanism for how viruses evade innate immunity.

Published
2019
Full Text
View/download PDF

219. T-cell trafficking plays an essential role in tumor immunity

Author

Aires, Daniel J., Yoshida, Masaru, Richardson, Stephen K., Bai, Mei, Liu, Luzheng, Moreno, Roberto, Lazar, Alexander J.F., Wick, Jo A., Rich, Benjamin E., Murphy, George, Blumberg, Richard S., Fuhlbrigge, Robert C., and Kupper, Thomas S.

Abstract

Distinct populations of effector memory T cells use different homing receptors to traffic to the skin and gut. Whether tissue-selective T cells are needed for early rejection of a neoplasm growing in these tissues remains an open question. We chose to study an allogeneic tumor model because growth of such a fully mismatched tumor would signify a profound immune deficit. We implanted allogeneic tumor cells in the skin or gut of mice deficient in either α(1,3) fucosyltransferases IV and VII, enzymes critical for generating E-selectin ligands on skin-homing T cells, or β7 integrin, a component of the α4β7 integrin ligand for the mucosal adressin MAdCAM. During the first 9 days after tumor implantation, FucTVII−/−mice showed a profoundly impaired capacity to reject tumors growing in the skin, but readily rejected tumors implanted in the gut. Rejection of tumors in the skin was even more impaired in mice deficient in both FucTIV and FucTVII. This impairment was corrected by infusion of T cells from normal mice. By contrast, β7 integrin−/−mice showed profoundly impaired rejection of tumors in the gut, but no defect in the skin tumor rejection. These differences were unrelated to antigen recognition or effector function of T cells, since all strains of mice were capable of generating tumor-specific CTLs in vitro against the tumor cell line used in vivo. These results demonstrate that T-cell homing defects in vivo impair immune surveillance of peripheral epithelial tissues in a specific and selective fashion.

Published
2019
Full Text
View/download PDF

220. Topical tofacitinib for the management of lymphocytic‐variant hypereosinophilic syndrome with cutaneous involvement.

Author

Said, Jordan T., Elman, Scott A., Tawa, Marianne, Fisher, David C., Merola, Joseph F., and Kupper, Thomas S.

Subjects
HYPEREOSINOPHILIC syndrome, T-cell receptor genes, CLONE cells
Abstract

The periorbital lesions were present at diagnosis; eyelid and thigh biopsies confirmed the clonal T-cell population and chronic dermal eosinophilic inflammation. The patient was diagnosed with L-HES 12 years prior to presentation; at diagnosis, T-cell receptor gene rearrangement sequencing of peripheral blood demonstrated a clonal CD3 SP - sp CD4 SP + sp CD5 SP + sp CD7 SP - sp CD8 SP - sp population, consistently present in the subsequent skin and lymph node biopsies. Prior systemic treatments for L-HES included prednisone, methotrexate, cyclophosphamide, alemtuzumab, brachytherapy, and vorinostat; the eyelid lesions only partially responded to each of these therapies. [Extracted from the article]

Published
2022
Full Text
View/download PDF

221. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

Author

Townsend, Elizabeth C., Murakami, Mark A., Christodoulou, Alexandra, Christie, Amanda L., Köster, Johannes, DeSouza, Tiffany A., Morgan, Elizabeth A., Kallgren, Scott P., Liu, Huiyun, Wu, Shuo-Chieh, Plana, Olivia, Montero, Joan, Stevenson, Kristen E., Rao, Prakash, Vadhi, Raga, Andreeff, Michael, Armand, Philippe, Ballen, Karen K., Barzaghi-Rinaudo, Patrizia, Cahill, Sarah, Clark, Rachael A., Cooke, Vesselina G., Davids, Matthew S., DeAngelo, Daniel J., Dorfman, David M., Eaton, Hilary, Ebert, Benjamin L., Etchin, Julia, Firestone, Brant, Fisher, David C., Freedman, Arnold S., Galinsky, Ilene A., Gao, Hui, Garcia, Jacqueline S., Garnache-Ottou, Francine, Graubert, Timothy A., Gutierrez, Alejandro, Halilovic, Ensar, Harris, Marian H., Herbert, Zachary T., Horwitz, Steven M., Inghirami, Giorgio, Intlekofer, Andrew M., Ito, Moriko, Izraeli, Shai, Jacobsen, Eric D., Jacobson, Caron A., Jeay, Sébastien, Jeremias, Irmela, Kelliher, Michelle A., Koch, Raphael, Konopleva, Marina, Kopp, Nadja, Kornblau, Steven M., Kung, Andrew L., Kupper, Thomas S., LeBoeuf, Nicole R., LaCasce, Ann S., Lees, Emma, Li, Loretta S., Look, A. Thomas, Murakami, Masato, Muschen, Markus, Neuberg, Donna, Ng, Samuel Y., Odejide, Oreofe O., Orkin, Stuart H., Paquette, Rachel R., Place, Andrew E., Roderick, Justine E., Ryan, Jeremy A., Sallan, Stephen E., Shoji, Brent, Silverman, Lewis B., Soiffer, Robert J., Steensma, David P., Stegmaier, Kimberly, Stone, Richard M., Tamburini, Jerome, Thorner, Aaron R., van Hummelen, Paul, Wadleigh, Martha, Wiesmann, Marion, Weng, Andrew P., Wuerthner, Jens U., Williams, David A., Wollison, Bruce M., Lane, Andrew A., Letai, Anthony, Bertagnolli, Monica M., Ritz, Jerome, Brown, Myles, Long, Henry, Aster, Jon C., Shipp, Margaret A., Griffin, James D., and Weinstock, David M.

Published
2016
Full Text
View/download PDF

223. CXCR4 pathway associated with family history of melanoma

Author

Li, Wen-Qing, primary, Han, Jiali, additional, Widlund, Hans R., additional, Correll, Mick, additional, Wang, Yaoyu E., additional, Quackenbush, John, additional, Mihm, Martin C., additional, Canales, Alvaro Laga, additional, Wu, Shaowei, additional, Golub, Todd, additional, Hoshida, Yujin, additional, Hunter, David J., additional, Murphy, George, additional, Kupper, Thomas S., additional, and Qureshi, Abrar A., additional

Published
2013
Full Text
View/download PDF

225. TH2 Cytokines from Malignant Cells Suppress TH1 Responses and Enforce a Global TH2 Bias in Leukemic Cutaneous T-cell Lymphoma

Author

Guenova, Emmanuella, primary, Watanabe, Rei, additional, Teague, Jessica E., additional, Desimone, Jennifer A., additional, Jiang, Ying, additional, Dowlatshahi, Mitra, additional, Schlapbach, Christoph, additional, Schaekel, Knut, additional, Rook, Alain H., additional, Tawa, Marianne, additional, Fisher, David C., additional, Kupper, Thomas S., additional, and Clark, Rachael A., additional

Published
2013
Full Text
View/download PDF

230. PGC-1 Coactivators Regulate MITF and the Tanning Response

Author

Shoag, Jonathan, primary, Haq, Rizwan, additional, Zhang, Mingfeng, additional, Liu, Laura, additional, Rowe, Glenn C., additional, Jiang, Aihua, additional, Koulisis, Nicole, additional, Farrel, Caitlin, additional, Amos, Christopher I., additional, Wei, Qingyi, additional, Lee, Jeffrey E., additional, Zhang, Jiangwen, additional, Kupper, Thomas S., additional, Qureshi, Abrar A., additional, Cui, Rutao, additional, Han, Jiali, additional, Fisher, David E., additional, and Arany, Zoltan, additional

Published
2013
Full Text
View/download PDF

231. Humanization of an Anti-CCR4 Antibody That Kills Cutaneous T-Cell Lymphoma Cells and Abrogates Suppression by T-Regulatory Cells

Author

Chang, De-Kuan, primary, Sui, Jianhua, additional, Geng, Shusheng, additional, Muvaffak, Asli, additional, Bai, Mei, additional, Fuhlbrigge, Robert C., additional, Lo, Agnes, additional, Yammanuru, Anuradha, additional, Hubbard, Luke, additional, Sheehan, Jared, additional, Campbell, James J., additional, Zhu, Quan, additional, Kupper, Thomas S., additional, and Marasco, Wayne A., additional

Published
2012
Full Text
View/download PDF

238. Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients

Author

Clark, Rachael A., primary, Watanabe, Rei, additional, Teague, Jessica E., additional, Schlapbach, Christoph, additional, Tawa, Marianne C., additional, Adams, Natalie, additional, Dorosario, Andrew A., additional, Chaney, Keri S., additional, Cutler, Corey S., additional, LeBoeuf, Nicole R., additional, Carter, Joi B., additional, Fisher, David C., additional, and Kupper, Thomas S., additional

Published
2012
Full Text
View/download PDF

239. A primary role for human central memory cells in tissue immunosurveillance

Author

Gehad, Ahmed, Teague, Jessica E., Matos, Tiago R., Huang, Victor, Yang, Chao, Watanabe, Rei, O'Malley, John T., Trimble, Cornelia L., Kupper, Thomas S., and Clark, Rachael A.

Abstract

Central memory T cells (TCM) patrol lymph nodes, providing central immunosurveillance against known pathogens, but have not been described as conducting primary tissue immunosurveillance. We analyzed the expression of tissue-homing addressins in human TCMvs effector memory T cells (TEM) from the same donors. In humans, the majority of human TCMwere tropic for either skin or gut, and the overall tissue tropism of TCMwas comparable to that of TEM. TCMwere present in healthy, noninflamed human skin, lung, colon, and cervix, suggesting a role for TCMin the primary immunosurveillance of peripheral tissues. TCMalso had potent effector functions; 80% of CD8+TCMproduced TC1/TC2/TC17/TC22 cytokines. TCMinjected into human skin–grafted mice migrated into skin and induced inflammatory eruptions comparable to TEM-injected mice. In summary, human TCMexpress peripheral tissue-homing receptors at levels similar to their effector memory counterparts, are found in healthy human tissues, have impressive effector functions, and can act alone to induce skin inflammation in human engrafted mice. Our studies support a novel role for human TCMin primary immunosurveillance of peripheral tissues and highlight the important role of this long-lived cell type in tissue-based immune responses.

Published
2018
Full Text
View/download PDF

240. VEGFR-1 Expressed by Malignant Melanoma-Initiating Cells Is Required for Tumor Growth

Author

Frank, Natasha Y., primary, Schatton, Tobias, additional, Kim, Soo, additional, Zhan, Qian, additional, Wilson, Brian J., additional, Ma, Jie, additional, Saab, Karim R., additional, Osherov, Veronika, additional, Widlund, Hans R., additional, Gasser, Martin, additional, Waaga-Gasser, Ana-Maria, additional, Kupper, Thomas S., additional, Murphy, George F., additional, and Frank, Markus H., additional

Published
2011
Full Text
View/download PDF

246. Interleukin-16 as a Marker of Sézary Syndrome Onset and Stage

Author

Richmond, Jillian, primary, Tuzova, Marina, additional, Parks, Ashley, additional, Adams, Natalie, additional, Martin, Elizabeth, additional, Tawa, Marianne, additional, Morrison, Lynne, additional, Chaney, Keri, additional, Kupper, Thomas S., additional, Curiel-Lewandrowski, Clara, additional, and Cruikshank, William, additional

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results