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Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma
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Abstract
Disabling the function of immune checkpoint molecules can unlock T-cell immunity against cancer, yet despite remarkable clinical success with monoclonal antibodies (mAb) that block PD-1 or CTLA-4, resistance remains common and essentially unexplained. To date, pancreatic carcinoma is fully refractory to these antibodies. Here, using a genetically engineered mouse model of pancreatic ductal adenocarcinoma in which spontaneous immunity is minimal, we found that PD-L1 is prominent in the tumor microenvironment, a phenotype confirmed in patients; however, tumor PD-L1 was found to be independent of IFNγ in this model. Tumor T cells expressed PD-1 as prominently as T cells from chronically infected mice, but treatment with αPD-1 mAbs, with or without αCTLA-4 mAbs, failed in well-established tumors, recapitulating clinical results. Agonist αCD40 mAbs with chemotherapy induced T-cell immunity and reversed the complete resistance of pancreatic tumors to αPD-1 and αCTLA-4. The combination of αCD40/chemotherapy plus αPD-1 and/or αCTLA-4 induced regression of subcutaneous tumors, improved overall survival, and conferred curative protection from multiple tumor rechallenges, consistent with immune memory not otherwise achievable. Combinatorial treatment nearly doubled survival of mice with spontaneous pancreatic cancers, although no cures were observed. Our findings suggest that in pancreatic carcinoma, a nonimmunogenic tumor, baseline refractoriness to checkpoint inhibitors can be rescued by the priming of a T-cell response with αCD40/chemotherapy. Cancer Immunol Res; 3(4); 399–411. ©2015 AACR.
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“Not surprisingly, therefore, the first clinical hints of success at deploying immunotherapy in PDAC have thus come from regimens that combine chemotherapy with targeting of one or more additional nodes within the dysfunctional TME (myeloid cells, Tregs) in combination with immune checkpoint inhibitors286,287.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [287]
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Conroy, T., Desseigne, F., Ychou, M., Bouché, O., Guimbaud, R., Bécouarn, Y., Adenis, A., Raoul, J.-L., Gourgou-Bourgade, S., de la Fouchardière, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011923 · Cited by 7,810
Rahib, L., Smith, B. D., Aizenberg, R., Rosenzweig, A. B., Fleshman, J. M., & Matrisian, L. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0155 · Cited by 7,094
Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine
Von Hoff, D. D., Ervin, T., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M., Seay, T., Tjulandin, S. A., Ma, W. W., Saleh, M. N., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1304369 · Cited by 6,712
Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011) · Science · doi:10.1126/science.1203486 · Cited by 6,474
PD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057
Self-citationCore Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969
Enhancement of Antitumor Immunity by CTLA-4 Blockade
Leach, D. R., Krummel, M. F., & Allison, J. P. (1996) · Science · doi:10.1126/science.271.5256.1734 · Cited by 3,955
Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma
Hamid, O., Robert, C., DAUD, A. I., Hodi, F. S., Hwu, W., Kefford, R. F., Wolchok, J. D., Hersey, P., Joseph, R. W., Weber, J. S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1305133 · Cited by 3,427
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170
Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
Powles, T. B., Eder, J. P., Fine, G. D., Braiteh, F. S., Loriot, Y., Cruz, C., Joaquim Bellmunt, B., Burris, H. A., Petrylak, D. P., Teng, S.-L. M., et al. (2014) · Nature · doi:10.1038/nature13904 · Cited by 2,410
Taube, J. M., Klein, A., Brahmer, J. R., Xu, H., Pan, X., Kim, J. H., Chen, L., Pardoll, D. M., Topalian, S. L., & Anders, R. A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3271 · Cited by 2,324
Provenzano, P. P., Cuevas, C., Chang, A. E., Goel, V. K., Von Hoff, D. D., & Hingorani, S. R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.01.007 · Cited by 2,195
Taube, J. M., Anders, R. A., Young, G. D., Xu, H., Sharma, R., McMiller, T. L., Chen, S., Klein, A. P., Pardoll, D. M., Topalian, S. L., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003689 · Cited by 2,157
EMT and Dissemination Precede Pancreatic Tumor Formation
Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F., Reichert, M., Beatty, G. L., Rustgi, A. K., Vonderheide, R. H., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.025 · Cited by 2,136
Self-citationMolecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
Self-citationFeig, C., Jones, J. O., Kraman, M., Wells, R. J. B., Deonarine, A., Chan, D. S., Connell, C. M., Roberts, E. W., Zhao, Q., Caballero, O. L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320318110 · Cited by 2,100
Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma
Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., Dekleva, E. N., Saunders, T., Becerra, C. P., Tattersall, I. W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.021 · Cited by 2,085
Self-citationBlackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062
Self-citationCurran, M. A., Montalvo, W., Yagita, H., & Allison, J. P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915174107 · Cited by 1,874
Autoimmune Dilated Cardiomyopathy in PD-1 Receptor-Deficient Mice
Nishimura, H., Okazaki, T., Tanaka, Y., Nakatani, K., Hara, M., Matsumori, A., Sasayama, S., Mizoguchi, A., Hiai, H., Minato, N., et al. (2001) · Science · doi:10.1126/science.291.5502.319 · Cited by 1,868
CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans
Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D., Song, W., Li, D., Sharp, L. L., et al. (2011) · Science · doi:10.1126/science.1198443 · Cited by 1,706
Self-citationSpranger, S., Spaapen, R. M., Zha, Y., Williams, J., Meng, Y., Ha, T. T., & Gajewski, T. F. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006504 · Cited by 1,677
Molecular mechanism and function of CD40/CD40L engagement in the immune system
Elgueta, R., Benson, M. J., de Vries, V. C., Wasiuk, A., Guo, Y., & Noelle, R. J. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00782.x · Cited by 1,633
Simpson, T. R., Li, F., Montalvo-Ortiz, W., Sepulveda, M. A., Bergerhoff, K., Arce, F., Roddie, C., Henry, J. Y., Yagita, H., Wolchok, J. D., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20130579 · Cited by 1,472
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.11.006 · Cited by 1,355
Self-citationZhu, Y., Knolhoff, B. L., Meyer, M. A., Nywening, T. M., West, B. L., Luo, J., Wang-Gillam, A., Goedegebuure, S. P., Linehan, D. C., & DeNardo, D. G. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3723 · Cited by 1,324
Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity
Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C., et al. (2003) · Nature Medicine · doi:10.1038/nm863 · Cited by 1,314
Royal, R. E., Levy, C. L., Turner, K. M., Mathur, A., Hughes, M. S., Kammula, U. S., Sherry, R. M., Topalian, S. L., Yang, J. C.-H., Lowy, I., et al. (2010) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181eec14c · Cited by 1,266
Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors
Akbay, E. A., Koyama, S., Carretero, J., Altabef, A. B., Tchaicha, J. H., Christensen, C. L., Mikse, O. R., Cherniack, A. D., Beauchamp, E. M., Pugh, T. J., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0310 · Cited by 1,250
Sherman, M. H., Yu, R. T., Engle, D. D., Ding, N., Atkins, A. R., Tiriac, H., Collisson, E. A., Connor, F., Van Dyke, T., Kozlov, S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.007 · Cited by 1,158
Self-citationHyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer
Jacobetz, M. A., Chan, D. S., Neesse, A., Bapiro, T. E., Cook, N., Frese, K. K., Feig, C., Nakagawa, T., Caldwell, M. E., Zecchini, H. I., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-302529 · Cited by 1,120
Dynamics of the immune reaction to pancreatic cancer from inception to invasion
Clark, C. E., Hingorani, S. R., Mick, R., Combs, C., Tuveson, D. A., & Vonderheide, R. H. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0175 · Cited by 990
Self-citationPeggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J., & Allison, J. P. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082492 · Cited by 967
Bayne, L. J., Beatty, G. L., Jhala, N., Clark, C. E., Rhim, A. D., Stanger, B. Z., & Vonderheide, R. H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.025 · Cited by 947 · cited 4×
“This model recapitulates the molecular, histologic and immune parameters of the human disease (39-43).”
BackgroundMethodInfluentialSelf-citationProgenitor and Terminal Subsets of CD8 + T Cells Cooperate to Contain Chronic Viral Infection
Paley, M., Kroy, D. C., Odorizzi, P. M., Johnnidis, J. B., Dolfi, D. V., Barnett, B. E., Bikoff, E. K., Robertson, E. J., Lauer, G. M., Reiner, S. L., et al. (2012) · Science · doi:10.1126/science.1229620 · Cited by 903
Self-citationNomi, T., Sho, M., Akahori, T., Hamada, K., Kubo, A., Kanehiro, H., Nakamura, S., Enomoto, K., Yagita, H., Azuma, M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2746 · Cited by 889
The Continuum of Cancer Immunosurveillance: Prognostic, Predictive, and Mechanistic Signatures
Galon, J., Angell, H. K., Bedognetti, D., & Marincola, F. M. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.008 · Cited by 887
Selby, M. J., Engelhardt, J. J., Quigley, M., Henning, K. A., Chen, T., Srinivasan, M., & Korman, A. J. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0013 · Cited by 857
Hiraoka, N., Onozato, K., Kosuge, T., & Hirohashi, S. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0369 · Cited by 849
Lyford-Pike, S., Peng, S., Young, G. D., Taube, J. M., Westra, W. H., Akpeng, B., Bruno, T. C., Richmon, J. D., Wang, H., Bishop, J. A., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2384 · Cited by 787
An immune-active tumor microenvironment favors clinical response to ipilimumab
Ji, R., Chasalow, S. D., Wang, L., Hamid, O., Schmidt, H., Cogswell, J. P., Alaparthy, S., Berman, D., Jure‐Kunkel, M., Siemers, N. O., et al. (2011) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-011-1172-6 · Cited by 783
Programmed death ligand-1 expression in non-small cell lung cancer
Velcheti, V., Schalper, K. A., Carvajal, D. E., Anagnostou, V., Syrigos, K. N., Sznol, M., Herbst, R. S., Gettinger, S. N., Chen, L., & Rimm, D. L. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.130 · Cited by 758
Duraiswamy, J., Kaluza, K. M., Freeman, G. J., & Coukos, G. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4100 · Cited by 753
Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia
Pylayeva-Gupta, Y., Lee, K. E., Hajdu, C. H., Miller, G., & Bar-Sagi, D. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.024 · Cited by 721 · cited 1×
“Potential other immunosuppressive pathways contributing to treatment resistance include myeloid-derived suppressor cells (MDSC), macrophages, and fibroblast-activating protein (FAP) mesenchymal cells, among others (43,65,66,69).”
BackgroundMonte, L. B. D., Reni, M., Tassi, E., Clavenna, D., Papa, I., Recalde, H. R., Braga, M., Carlo, V. D., Doglioni, C., & Protti, M. P. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101876 · Cited by 721
Zamarin, D., Holmgaard, R. B., Subudhi, S. K., Park, J. S., Mansour, M., Palese, P., Merghoub, T., Wolchok, J. D., & Allison, J. P. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008095 · Cited by 711
Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade
Blackburn, S. D., Shin, H., Freeman, G. J., & Wherry, E. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801497105 · Cited by 593
Self-citationLe, D. T., Lutz, E. R., Uram, J. N., Sugar, E. A., Onners, B., Solt, S., Zheng, L., Diaz, L. A., Donehower, R. C., Jaffee, E. M., et al. (2013) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31829fb7a2 · Cited by 566
Doering, T. A., Crawford, A., Angelosanto, J., Paley, M., Ziegler, C. G. K., & Wherry, E. J. (2012) · Immunity · doi:10.1016/j.immuni.2012.08.021 · Cited by 563
Self-citationImmunotherapy Converts Nonimmunogenic Pancreatic Tumors into Immunogenic Foci of Immune Regulation
Lutz, E. R., Wu, A. A., Bigelow, E. O., Sharma, R. B., Mo, G., Soares, K. C., Solt, S., Dorman, A., Wamwea, A., Yager, A., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0027 · Cited by 560
Fukunaga, A., Miyamoto, M., Cho, Y., Murakami, S., Kawarada, Y., Oshikiri, T., Kato, K., Kurokawa, T., Suzuoki, M., Nakakubo, Y., et al. (2003) · Pancreas · doi:10.1097/00006676-200401000-00023 · Cited by 532
Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer—Response
Sznol, M., & Chen, L. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2234 · Cited by 532
Immune Modulation in Cancer with Antibodies
Page, D. B., Postow, M. A., Callahan, M. K., Allison, J. P., & Wolchok, J. D. (2013) · Annual Review of Medicine · doi:10.1146/annurev-med-092012-112807 · Cited by 523
Molecular and Transcriptional Basis of CD4+ T Cell Dysfunction during Chronic Infection
Crawford, A., Angelosanto, J., Kao, C., Doering, T. A., Odorizzi, P. M., Barnett, B. E., & Wherry, E. J. (2014) · Immunity · doi:10.1016/j.immuni.2014.01.005 · Cited by 513
Self-citationAntagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer
Sznol, M., & Chen, L. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2063 · Cited by 501
Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors.
Nowak, A. K., Robinson, B. W. S., & Lake, R. (2003) · PubMed · Cited by 414
Soares, K. C., Rucki, A. A., Wu, A. A., Olino, K. L., Xiao, Q., Chai, Y., Wamwea, A., Bigelow, E. O., Lutz, E. R., Liu, L. L., et al. (2014) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000062 · Cited by 406
Anti–CTLA-4 therapy broadens the melanoma-reactive CD8 + T cell response
Kvistborg, P., Philips, D., Kelderman, S., Hageman, L., Ottensmeier, C. H. H., Joseph‐Pietras, D., Welters, M. J. P., van der Burg, S., Kapiteijn, E., Michielin, O. A., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008918 · Cited by 392
Systemic and local immunosuppression in pancreatic cancer patients.
von Bernstorff, W., Voss, M., Freichel, S., Schmid, A., Vogel, I., Jöhnk, C., Henne‐Bruns, D., Kremer, B., & Kalthoff, H. (2001) · PubMed · Cited by 279
Immune Cell–Poor Melanomas Benefit from PD-1 Blockade after Targeted Type I IFN Activation
Bald, T., Landsberg, J., Lopez-Ramos, D., Renn, M., Glodde, N., Jansen, P., Gaffal, E., Steitz, J., Tolba, R. H., Kalinke, U., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0458 · Cited by 261
Gajewski, T. F., Louahed, J., & Brichard, V. G. (2010) · The Cancer Journal · doi:10.1097/ppo.0b013e3181eacbd8 · Cited by 250
Inflammatory networks and immune surveillance of pancreatic carcinoma
Vonderheide, R. H., & Bayne, L. J. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.01.006 · Cited by 204
Self-citationEnhanced Tumor Eradication by Combining CTLA-4 or PD-1 Blockade With CpG Therapy
Mangsbo, S. M., Sandin, L. C., Anger, K., Korman, A. J., Loskog, A., & Tötterman, T. H. (2010) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181c01fcb · Cited by 198
Inhibitory Receptors on Lymphocytes: Insights from Infections
Odorizzi, P. M., & Wherry, E. J. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1100038 · Cited by 175
Self-citationClark, C. E., Beatty, G. L., & Vonderheide, R. H. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.09.037 · Cited by 160
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Metadata
- Authors
- Winograd, R., Byrne, K. T., Evans, R. A., Odorizzi, P. M., Meyer, A. R. L., Bajor, D. L., Clendenin, C., Stanger, B. Z., Furth, E. E., Wherry, E. J., & Vonderheide, R. H.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Vonderheide, Robert H.
- ORCID
- Venue
- Cancer Immunology Research
- Published
- 2015-04-01
- Volume
- 3
- Issue
- 4
- Pages
- 399-411
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- PMC
- PMC4390506
- OpenAlex
- W2132290857
- Cited by
- 459
- References
- 87
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 27 · 2023: 44 · 2022: 42 · 2021: 78 · 2020: 53 · 2019: 51 · 2018: 40 · 2017: 37 · 2016: 33 · 2015: 11
- FWCI
- 17.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Immunology Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- York University
- National Heart, Lung, and Blood Institute (T32HL007775, T32HL007439)
- National Cancer Institute (T32CA009140, R01CA169123, P30CA016520)
- National Institute of Allergy and Infectious Diseases (P01AI112521, U19AI082630)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- pancreatic ductal adenocarcinoma, anti-PD-1 therapy, CTLA-4 blockade, immune checkpoint inhibitors, treatment resistance, PD-L1, tumor microenvironment, T cell immunity, combination chemotherapy, tumor immunogenicity, immunological memory, genetically engineered mouse models
- MeSH terms
- Gemcitabine, Animals, Antibodies, Monoclonal, Antimetabolites, Antineoplastic, Combined Modality Therapy, Deoxycytidine, Female, Genetic Engineering, Humans, Immune Tolerance, Immunity, Cellular, Interferon-gamma, Lymphocyte Activation, Mice, Inbred C57BL, Pancreatic Neoplasms, T-Lymphocyte Subsets, CD40 Antigens, Carcinoma, Pancreatic Ductal, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Microenvironment, B7-H1 Antigen, CTLA-4 Antigen
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