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PD-1 Blockade Enhances T-cell Migration to Tumors by Elevating IFN-γ Inducible Chemokines
Open accessPublished version of a preprint
Abstract
Adoptive cell transfer (ACT) is considered a promising modality for cancer treatment, but despite ongoing improvements, many patients do not experience clinical benefits. The tumor microenvironment is an important limiting factor in immunotherapy that has not been addressed fully in ACT treatments. In this study, we report that upregualtion of the immunosuppressive receptor programmed cell death-1 (PD-1) expressed on transferred T cells at the tumor site, in a murine model of ACT, compared with its expression on transferred T cells present in the peripheral blood and spleen. As PD-1 can attenuate T-cell-mediated antitumor responses, we tested whether its blockade with an anti-PD-1 antibody could enhance the antitumor activity of ACT in this model. Cotreatment with both agents increased the number of transferred T cells at the tumor site and also enhanced tumor regressions, compared with treatments with either agent alone. While anti-PD-1 did not reduce the number of immunosuppressive regulatory T cells and myeloid-derived suppressor cells present in tumor-bearing mice, we found that it increased expression of IFN-γ and CXCL10 at the tumor site. Bone marrow-transplant experiments using IFN-γR-/- mice implicated IFN-γ as a crucial nexus for controlling PD-1-mediated tumor infiltration by T cells. Taken together, our results imply that blocking the PD-1 pathway can increase IFN-γ at the tumor site, thereby increasing chemokine-dependent trafficking of immune cells into malignant disease sites.
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“Indeed, mouse models have shown that local IFN-γ upregulation is essential for anti-PD-1-mediated tumor regression (89).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [89]
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Cites
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
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
Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia
Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103849 · Cited by 3,565
Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,259
Brahmer, J. R., Drake, C. G., WOLLNER, I. S., Powderly, J. D., Picus, J., Sharfman, W. H., Stankevich, E., Pons, A., Salay, T. M., McMiller, T. L., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.7609 · Cited by 2,967
Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80089-8 · Cited by 2,749
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680
CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms
Parry, R. V., Chemnitz, J. M., Frauwirth, K. A., Lanfranco, A. R., Braunstein, I., Kobayashi, S. V., Linsley, P. S., Thompson, C. B., & Riley, J. L. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9543-9553.2005 · Cited by 1,931
Curran, 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
Self-citationExpression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes
Agata, Y., Kawasaki, A., Nishimura, H., Ishida, Y., Tsubat, T., Yagita, H., & Honjo, T. (1996) · International Immunology · doi:10.1093/intimm/8.5.765 · Cited by 1,589
Self-citationUpregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
Trautmann, L., Janbazian, L., Chomont, N., Said, E. A., Gimmig, S., Bessette, B., Boulassel, M.-R., Delwart, E., Sepulveda, H., Balderas, R. S., et al. (2006) · Nature Medicine · doi:10.1038/nm1482 · Cited by 1,565
Pulè, M. A., Savoldo, B., Myers, G. D., Rössig, C., Russell, H. V., Dotti, G., Huls, M. H., Liu, E., Gee, A. P., Mei, Z., et al. (2008) · Nature Medicine · doi:10.1038/nm.1882 · Cited by 1,195
Nomi, 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
Self-citationThompson, R. H., Gillett, M. D., Cheville, J. C., Lohse, C. M., Dong, H., Webster, W. S., Krejci, K. G., Lobo, J. R., Sengupta, S., Chen, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406351101 · Cited by 776
Blank, C., Brown, I., Peterson, A. C., Spiotto, M., Iwai, Y., Honjo, T., & Gajewski, T. F. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3259 · Cited by 772
Till, B. G., Jensen, M. C., Wang, J., Chen, E., Wood, B. L., Greisman, H. A., Qian, X., James, S. E., Raubitschek, A. A., Forman, S. J., et al. (2008) · Blood · doi:10.1182/blood-2007-12-128843 · Cited by 721
Berger, R., Rotem‐Yehudar, R., Slama, G., Landes, S., Kneller, A., Leiba, M., Koren‐Michowitz, M., Shimoni, A., & Nagler, A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4079 · Cited by 691
Biochemical characterization of a gamma interferon-inducible cytokine (IP-10)
Luster, A., & Ravetch, J. (1987) · Journal of Experimental Medicine · doi:10.1084/jem.166.4.1084 · Cited by 676
Hino, R., Kabashima, K., Kato, Y., Yagi, H., Nakamura, M., Honjo, T., Okazaki, T., & TOKURA, Y. (2010) · Cancer · doi:10.1002/cncr.24899 · Cited by 668
Blank, C. U., Gajewski, T. F., & Mackensen, A. (2004) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-004-0593-x · Cited by 656
Thompson, R. H., Dong, H., Lohse, C. M., Leibovich, B. C., Blute, M. L., Cheville, J. C., & Kwon, E. D. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2599 · Cited by 569
Establishment of NOD- Pdcd1 -/- mice as an efficient animal model of type I diabetes
Wang, J., Yoshida, T., Nakaki, F., Hiai, H., Okazaki, T., & Honjo, T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505497102 · Cited by 450
Thompson, R. H., Gillett, M. D., Cheville, J. C., Lohse, C. M., Dong, H., Webster, W. S., Krejci, K. G., Lobo, J. R., Sengupta, S., Chen, L., et al. (2005) · The Journal of Urology · doi:10.1016/s0022-5347(18)34858-4 · Cited by 386
The role of the PD‐1 pathway in autoimmunity and peripheral tolerance
Fife, B. T., & Pauken, K. E. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05919.x · Cited by 366
Fisher, B., Packard, B. S., Read, E. J., Carrasquillo, J. A., Carter, C. S., Topalian, S. L., Yang, J., Yolles, P., Larson, S. M., & Rosenberg, S. A. (1989) · Journal of Clinical Oncology · doi:10.1200/jco.1989.7.2.250 · Cited by 327
Karim, R., Jordanova, E. S., Piersma, S. J., Kenter, G. G., Chen, L., Boer, J. M., Melief, C. J. M., & van der Burg, S. H. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1652 · Cited by 253
Zhang, Y., Huang, S., Gong, D., Qin, Y., & Shen, Q. (2010) · Cellular and Molecular Immunology · doi:10.1038/cmi.2010.28 · Cited by 243
Peng, W., Ye, Y., Rabinovich, B. A., Liu, C., Lou, Y., Zhang, M., Whittington, M., Yang, Y., Overwijk, W. W., Lizee, G. A., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0712 · Cited by 222
Self-citationGriffith, K. D., Read, E. J., Carrasquillo, J. A., Carter, C. S., Yang, J. C.-H., Fisher, B., Aebersold, P. M., Packard, B. S., Yu, M. Y., & Rosenberg, S. A. (1989) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/81.22.1709 · Cited by 182
Mkrtichyan, M., Najjar, Y. G., Raulfs, E. C., Abdalla, M. Y., Samara, R. N., Rotem‐Yehudar, R., Cook, L., & Khleif, S. N. (2011) · European Journal of Immunology · doi:10.1002/eji.201141639 · Cited by 144
Yamazaki, T., Akiba, H., Koyanagi, A., Azuma, M., Yagita∥, H., & Okumura, K. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.3.1586 · Cited by 139
Self-citationHeemskerk, B., Liu, K., Dudley, M. E., Johnson, L. A., Kaiser, A., Downey, S. G., Zheng, Z., Shelton, T. E., Matsuda, K. M., Robbins, P. F., et al. (2008) · Human Gene Therapy · doi:10.1089/hum.2007.0171 · Cited by 136
Improving Antitumor Immune Responses by Circumventing Immunoregulatory Cells and Mechanisms
Lizee, G. A., Radvanyi, L. G., Overwijk, W. W., & Hwu, P. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0944 · Cited by 109
Self-citationEarly T Cell Signalling Is Reversibly Altered in PD-1+ T Lymphocytes Infiltrating Human Tumors
Renault, S., Fouquet, S., Chapon, M., Salmon, H., Régnier, F., Labroquère, K., Badoual, C., Damotte, D., Validire, P., Maubec, E., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017621 · Cited by 92
Chapon, M., Randriamampita, C., Maubec, E., Badoual, C., Fouquet, S., Wang, S.-F., Marinho, E., Farhi, D., Garcette, M., Jacobelli, S., et al. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.30 · Cited by 86
Development of Adoptive Cell Therapy for Cancer: A Clinical Perspective
Hawkins, R. E., Gilham, D. E., Debets, R., Eshhar, Z., Taylor, N. N., Abken, H., & Schumacher, T. N. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.086 · Cited by 79
Sierro, S. R., Donda, A., Perret, R., Guillaume, P., Yagita∥, H., Lévy, F., & Romero, P. J. (2011) · European Journal of Immunology · doi:10.1002/eji.201041235 · Cited by 74
Self-citationZhou, Q., Xiao, H., Liu, Y., Peng, Y., Yuan, H., Yagita∥, H., Chandler, P., Munn, D. H., Mellor, A. L., Fu, N., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001821 · Cited by 62
Self-citationZhang, M., Maiti, S. N., Bernatchez, C., Huls, H. M., Rabinovich, B. A., Champlin, R. E., Vence, L. M., Hwu, P., Radvanyi, L. G., & Cooper, L. J. N. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3234 · Cited by 21
Self-citationPeddareddigari, V. G. R., MILLER, P. W., Nebiyou, B. B., Overwijk, W. W., Ross, M. I., Lee, J., Gershenwald, J. E., Prieto, V. G., Hwu, P., & Radvanyi, L. G. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.3021 · Cited by 1
Self-citation
Research works printed but not linked: 1
- Laszlo, 2010, Adoptive T cell therapy for metastatic melanoma: the MD Anderson experience, J Immunother, 33, 863
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Spranger, S., Bao, R., & Gajewski, T. F. (2015) · Nature · doi:10.1038/nature14404 · Cited by 2,830
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Tokunaga, R., Zhang, W., Naseem, M., Puccini, A., Berger, M. D., Soni, S., McSkane, M., Baba, H., & Lenz, H.-J. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.11.007 · Cited by 1,627
IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy
Ivashkiv, L. B. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0029-z · Cited by 1,418
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Seidel, J. A., Otsuka, A., & Kabashima, K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00086 · Cited by 1,360
Metadata
- Authors
- Peng, W., Liu, C., Xu, C., Lou, Y., Chen, J., Yang, Y., Yagita, H., Overwijk, W. W., Lizée, G., Radvanyi, L., & Hwu, P.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Authors' Affiliations: 1Department of Melanoma Medical Oncology, The Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas; and 2Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
- Corresponding author
- Hwu, Patrick
- ORCID
- Venue
- Cancer Research
- Published
- 2012-10-14
- Volume
- 72
- Issue
- 20
- Pages
- 5209-5218
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3476734
- OpenAlex
- W2116158418
- Cited by
- 432
- References
- 41
- Citations by year
- 2026: 18 · 2025: 25 · 2024: 27 · 2023: 38 · 2022: 47 · 2021: 31 · 2020: 30 · 2019: 40 · 2018: 38 · 2017: 34 · 2016: 33 · 2015: 34 · 2014: 17 · 2013: 18 · 2012: 2
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Japan Society for the Promotion of Science (22240089)
- National Cancer Institute (R01CA143077, CA 016672, R01CA123182, P01CA128913, R01CA116206, P30CA016672)
- National Center for Research Resources (UL1RR024148)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- anti-PD-1 therapy, adoptive cell transfer, interferon-gamma, CXCL10, chemokines, tumor microenvironment, regulatory T cells, myeloid-derived suppressor cells, IFN-gamma receptor, antitumor immunity, immune cell trafficking
- MeSH terms
- Animals, Cell Movement, Interferon-gamma, Mice, Transgenic, Neoplasms, Experimental, T-Lymphocytes, Up-Regulation, Lymphocytes, Tumor-Infiltrating, Chemokines, Adoptive Transfer, Cell Proliferation, Mice, Programmed Cell Death 1 Receptor
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