T-cell invigoration to tumour burden ratio associated with anti-PD-1 response
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Despite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. Pre-existing T-cell infiltration and/or the presence of PD-L1 in tumours may be used as indicators of clinical response; however, blood-based profiling to understand the mechanisms of PD-1 blockade has not been widely explored. Here we use immune profiling of peripheral blood from patients with stage IV melanoma before and after treatment with the PD-1-targeting antibody pembrolizumab and identify pharmacodynamic changes in circulating exhausted-phenotype CD8 T cells (T ex cells). Most of the patients demonstrated an immunological response to pembrolizumab. Clinical failure in many patients was not solely due to an inability to induce immune reinvigoration, but rather resulted from an imbalance between T-cell reinvigoration and tumour burden. The magnitude of reinvigoration of circulating T ex cells determined in relation to pretreatment tumour burden correlated with clinical response. By focused profiling of a mechanistically relevant circulating T-cell subpopulation calibrated to pretreatment disease burden, we identify a clinically accessible potential on-treatment predictor of response to PD-1 blockade.
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Proliferation of circulating CD8+PD-1hi CTLA-4+ T cells within 3-4 weeks of immune checkpoint inhibitor treatment was associated with responders in melanoma and NSCLC patients.
“proliferation of circulating CD8 + PD-1 hi CTLA-4 + T cells, within 3-4 weeks of ICI treatment, was also associated with responders in patients with melanoma and patients with NSCLC (148, 149).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [148]
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1 retracted
Host immunity contributes to the anti-melanoma activity of BRAF inhibitors
Knight, D. A., Ngiow, S. F., Li, M., Parmenter, T. J., Mok, S., Cass, A. A., Haynes, N. M., Kinross, K. M., Yagita∥, H., Koya, R. C., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66236 · Cited by 268 · see citing works
RetractedBreiman, L. (2001) · Machine Learning · doi:10.1023/a:1010933404324 · Cited by 133,538 · see citing works
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 · see citing works
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 15,314 · see citing works
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802 · see citing works
Self-citationPD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609 · see citing works
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887 · see citing works
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 · see citing works
The immune contexture in human tumours: impact on clinical outcome
Fridman, W. H., Pagès, F., Sautès-Fridman, C., & Galon, J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3245 · Cited by 4,981 · see citing works
Final Version of 2009 AJCC Melanoma Staging and Classification
Balch, C. M., Gershenwald, J. E., Soong, S.-J., Thompson, J. F., Atkins, M. B., Byrd, D. R., Buzaid, A. C., Cochran, A. J., Coit, D. G., Ding, S., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.4799 · Cited by 4,592 · see citing works
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229 · see citing works
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 3,960 · see citing works
Self-citationWolchok, J. D., Hoos, A., O'Day, S. J., Weber, J. S., Hamid, O., Lebbé, C., Maio, M., Binder, M., Bohnsack, O., Nichol, G. M., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1624 · Cited by 3,214 · see citing works
Self-citationBrahmer, 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 · see citing works
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy
Topalian, S. L., Taube, J. M., Anders, R. A., & Pardoll, D. M. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.36 · Cited by 2,733 · see citing works
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
Twyman-Saint Victor, C., Rech, A. J., Maity, A., Rengan, R., Pauken, K. E., Stelekati, E., Benci, J. L., Xu, B., Dada, H., Odorizzi, P. M., et al. (2015) · Nature · doi:10.1038/nature14292 · Cited by 2,434 · see citing works
Self-citationImmune checkpoint targeting in cancer therapy: toward combination strategies with curative potential
Sharma, P., & Allison, J. P. (2015) · Cell · doi:10.1016/j.cell.2015.03.030 · Cited by 2,345 · see citing works
Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy
Im, S. J., Hashimoto, M., Gerner, M. Y., Lee, J., Kissick, H. T., Burger, M. C., Shan, Q., Hale, J. S., Lee, J., Nasti, T. H., et al. (2016) · Nature · doi:10.1038/nature19330 · Cited by 2,070 · see citing works
Blackburn, 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 · see citing works
Self-citationWherry, E. J., Blattman, J. N., Murali‐Krishna, K., der Most, R. G. V., & Ahmed, R. (2003) · Journal of Virology · doi:10.1128/jvi.77.8.4911-4927.2003 · Cited by 1,599 · see citing works
Self-citationRibas, A., Puzanov, I. J., Dummer, R., Schadendorf, D., Hamid, O., Robert, C., Hodi, F. S., Schachter, J., Pavlick, A. C., Lewis, K. D., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00083-2 · Cited by 1,580 · see citing works
Self-citationEpigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade
Pauken, K. E., Sammons, M. A., Odorizzi, P. M., Manne, S., Godec, J., Khan, O., Drake, A. M., Chen, Z., Sen, D. R., Kurachi, M., et al. (2016) · Science · doi:10.1126/science.aaf2807 · Cited by 1,348 · see citing works
Self-citationOvercoming T cell exhaustion in infection and cancer
Pauken, K. E., & Wherry, E. J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.008 · Cited by 1,178 · see citing works
Self-citationExtracting a cellular hierarchy from high-dimensional cytometry data with SPADE
Qiu, P., Simonds, E. F., Bendall, S. C., Gibbs, K. D., Bruggner, R. V., Linderman, M. D., Sachs, K., Nolan, G. P., & Plevritis, S. K. (2011) · Nature Biotechnology · doi:10.1038/nbt.1991 · Cited by 956 · see citing works
Combination cancer immunotherapies tailored to the tumour microenvironment
Smyth, M. J., Ngiow, S. F., Ribas, A., & Teng, M. W. L. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.209 · Cited by 944 · see citing works
Progenitor 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 · see citing works
Self-citationGros, A., Parkhurst, M. R., Tran, E., Pasetto, A., Robbins, P. F., Ilyas, S., Prickett, T. D., Gartner, J. J., Crystal, J. S., Roberts, I. M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4051 · Cited by 830 · see citing works
Selective BRAF Inhibitors Induce Marked T-cell Infiltration into Human Metastatic Melanoma
Wilmott, J. S., Long, G. V., Howle, J. R., Haydu, L. E., Sharma, R. N., Thompson, J. F., Kefford, R. F., Hersey, P., & Scolyer, R. A. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2479 · Cited by 651 · see citing works
Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection
He, R., Hou, S., Liu, C., Zhang, A.-L., Bai, Q., Han, M., Yang, Y., Wei, G., Shen, T., Yang, X.-X., et al. (2016) · Nature · doi:10.1038/nature19317 · Cited by 643 · see citing works
Human Effector and Memory CD8+ T Cell Responses to Smallpox and Yellow Fever Vaccines
Miller, J. D., van der Most, R. G., Akondy, R. S., Glidewell, J. T., Albott, S., Masopust, D., Murali-Krishna, K., Mahar, P. L., Edupuganti, S., Lalor, S., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.020 · Cited by 601 · see citing works
Nishino, M., Giobbie-Hurder, A., Gargano, M., Suda, M., Ramaiya, N. H., & Hodi, F. S. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0895 · Cited by 522 · see citing works
CD39 Expression Identifies Terminally Exhausted CD8+ T Cells
Gupta, P., Godec, J., Wolski, D., Adland, E., Yates, K. B., Pauken, K. E., Cosgrove, C., Ledderose, C., JUNGER, W. G., Robson, S. C., et al. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1005177 · Cited by 384 · see citing works
Self-citationBengsch, B., Seigel, B., Ruhl, M., Timm, J., Kuntz, M., Blum, H. E., Pircher, H., & Thimme, R. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000947 · Cited by 373 · see citing works
Self-citationDuraiswamy, J., Ibegbu, C., Masopust, D., Miller, J. D., Araki, K., Doho, G., Tata, P., Sk, G., Zilliox, M. J., Nakaya, H. I., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001783 · Cited by 246 · see citing works
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Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response
Chen, G., Huang, A. C., Zhang, W., Zhang, G., Wu, M., Xu, W., Yu, Z., Yang, J., Wang, B., Sun, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0392-8 · Cited by 2,813 · see citing works
Self-citationDetection and localization of surgically resectable cancers with a multi-analyte blood test
Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., et al. (2018) · Science · doi:10.1126/science.aar3247 · Cited by 2,783 · see citing works
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709919 · Cited by 2,688 · see citing works
Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy
Cristescu, R., Mogg, R., Ayers, M., Albright, A., Murphy, E., Yearley, J., Sher, X., Liu, X. Q., Lu, H., Nebozhyn, M., et al. (2018) · Science · doi:10.1126/science.aar3593 · Cited by 2,301 · see citing works
The immune contexture in cancer prognosis and treatment
Fridman, W. H., Zitvogel, L., Sautès–Fridman, C., & Kroemer, G. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.101 · Cited by 2,263 · see citing works
Bagchi, S., Yuan, R., & Engleman, E. G. (2021) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-042020-042741 · Cited by 2,189 · see citing works
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma
Sade-Feldman, M., Yizhak, K., Bjorgaard, S. L., Ray, J. P., de Boer, C. G., Jenkins, R. W., Lieb, D. J., Chen, J. H., Frederick, D. T., Barzily-Rokni, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.038 · Cited by 2,053 · see citing works
Immunotherapies for hepatocellular carcinoma
Llovet, J. M., Castet, F., Heikenwalder, M., Maini, M. K., Mazzaferro, V., Pinato, D. J., Pikarsky, E., Zhu, A. X., & Finn, R. S. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00573-2 · Cited by 1,843 · see citing works
TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion
Khan, O., Giles, J. R., McDonald, S., Manne, S., Ngiow, S. F., Patel, K. P., Werner, M. T., Huang, A. C., Alexander, K. A., Wu, J. E., et al. (2019) · Nature · doi:10.1038/s41586-019-1325-x · Cited by 1,646 · see citing works
Self-citationMathew, D., Giles, J. R., Baxter, A. E., Oldridge, D. A., Greenplate, A. R., Wu, J. E., Alanio, C., Kuri-Cervantes, L., Pampena, M. B., D’Andrea, K., et al. (2020) · Science · doi:10.1126/science.abc8511 · Cited by 1,509 · see citing works
Self-citationOrganoid modeling of the tumor immune microenvironment
Neal, J. T., Li, X., Zhu, J., Giangarra, V., Grzeskowiak, C. L., Ju, J., Liu, I. H., Chiou, S.-H., Salahudeen, A. A., Smith, A. R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.11.021 · Cited by 1,556 · see citing works
CD4+ T cell help in cancer immunology and immunotherapy
Borst, J., Ahrends, T., Bąbała, N., Melief, C. J. M., & Kastenmüller, W. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0044-0 · Cited by 1,585 · see citing works
Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates
Simoni, Y., Becht, E., Fehlings, M., Loh, C. Y., Koo, S.-L., Teng, K. W. W., Yeong, J. P. S., Nahar, R., Zhang, T., Kared, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0130-2 · Cited by 1,370 · see citing works
Mechanisms of resistance to immune checkpoint inhibitors
Jenkins, R. W., Barbie, D. A., & Flaherty, K. T. (2018) · British Journal of Cancer · doi:10.1038/bjc.2017.434 · Cited by 1,383 · see citing works
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade
Wei, S. C., Levine, J. H., Cogdill, A. P., Zhao, Y., Anang, N.-A. A. S., Andrews, M. C., Sharma, P., Wang, J., Wargo, J. A., Pe’er, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.024 · Cited by 1,302 · see citing works
Lv, M., Chen, M., Zhang, R., Zhang, W., Wang, C., Zhang, Y., Wei, X., Guan, Y., Liu, J., Feng, K., et al. (2020) · Cell Research · doi:10.1038/s41422-020-00395-4 · Cited by 1,040 · see citing works
Garris, C. S., Arlauckas, S. P., Kohler, R. H., Trefny, M. P., Garren, S., Piot, C., Engblom, C., Pfirschke, C., Siwicki, M., Gungabeesoon, J., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.09.024 · Cited by 966 · see citing works
Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade
Hsu, J., Hodgins, J. J., Marathe, M., Nicolai, C. J., Bourgeois-Daigneault, M.-C., Trevino, T. N., Azimi, C. S., Scheer, A. K., Randolph, H. E., Thompson, T. W., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99317 · Cited by 817 · see citing works
TCF-1-centered transcriptional network drives an effector versus exhausted CD8 T cell-fate decision
Chen, Z., Ji, Z., Ngiow, S. F., Manne, S., Cai, Z., Huang, A. C., Johnson, J., Staupe, R. P., Bengsch, B., Xu, C., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.09.013 · Cited by 709 · see citing works
Chow, M. T., Ozga, A. J., Servis, R. L., Frederick, D. T., Lo, J. A., Fisher, D. E., Freeman, G. J., Boland, G. M., & Luster, A. D. (2019) · Immunity · doi:10.1016/j.immuni.2019.04.010 · Cited by 716 · see citing works
“The extent of enhancement of the CD8 T cell response by PD-1 blockade is one of the critical determinants of the efficacy of anti-PD-1 therapy (Huang et al., 2017).”
High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy
Krieg, C., Nowicka, M., Guglietta, S., Schindler, S., Hartmann, F. J., Weber, L. M., Dummer, R., Robinson, M. D., Levesque, M. P., & Becher, B. (2018) · Nature Medicine · doi:10.1038/nm.4466 · Cited by 735 · see citing works
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells
Kurtulus, S., Madi, A., Escobar, G., Klapholz, M., Nyman, J., Christian, E., Pawlak, M., Dionne, D., Xia, J., Rozenblatt-Rosen, O., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.11.014 · Cited by 636 · see citing works
Kloss, C. C., Lee, J., Zhang, A., Chen, F., Melenhorst, J. J., Lacey, S. F., Maus, M. V., Fraietta, J. A., Zhao, Y., & June, C. H. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.05.003 · Cited by 648 · see citing works
<i>Ex Vivo</i> Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids
Jenkins, R. W., Aref, A. R., Lizotte, P. H., Ivanova, E., Stinson, S., Zhou, C. W., Bowden, M., Deng, J., Liu, H., Miao, D., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0833 · Cited by 594 · see citing works
The hallmarks of successful anticancer immunotherapy
Galluzzi, L., Chan, T. A., Kroemer, G., Wolchok, J. D., & López-Soto, A. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat7807 · Cited by 575 · see citing works
Self-citationCombination Immunotherapy with CAR T Cells and Checkpoint Blockade for the Treatment of Solid Tumors
Grosser, R., Cherkassky, L., Chintala, N., & Adusumilli, P. S. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.09.006 · Cited by 603 · see citing works
Luke, J. J., Lemons, J. M., Karrison, T. G., Pitroda, S. P., Melotek, J. M., Zha, Y., Al-Hallaq, H. A., Arina, A., Khodarev, N. N., Janisch, L., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.76.2229 · Cited by 588 · see citing works
Benci, J. L., Johnson, L. R., Choa, R., Xu, Y., Qiu, J., Zhou, Z., Xu, B., Ye, D., Nathanson, K. L., June, C. H., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.019 · Cited by 541 · see citing works
Self-citationLXR/ApoE Activation Restricts Innate Immune Suppression in Cancer
Tavazoie, M. F., Pollack, I., Tanqueco, R., Ostendorf, B. N., Reis, B. S., Gonsalves, F. C., Kurth, I., Andreu-Agullo, C., Derbyshire, M. L., Posada, J., et al. (2018) · Cell · doi:10.1016/j.cell.2017.12.026 · Cited by 476 · see citing works
“…Figures 7G and 7H), consistent with this population of cells possessing the ‘‘exhausted’’ phenotype that has been associated with tumor-targeting cytotoxic T cells—the main target cell population activated with checkpoint blockade (Huang et al., 2017; Kamphorst et al., 2017; Wei et al., 2017).”
Self-citationWei, S. C., Anang, N.-A. A. S., Sharma, R., Andrews, M. C., Reuben, A., Levine, J. H., Cogdill, A. P., Mancuso, J. J., Wargo, J. A., Pe’er, D., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821218116 · Cited by 359 · see citing works
Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma
Llovet, J. M., Pinyol, R., Yarchoan, M., Singal, A. G., Marron, T. U., Schwartz, M., Pikarsky, E., Kudo, M., & Finn, R. S. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00868-0 · Cited by 391 · see citing works
Verma, V., Shrimali, R. K., Ahmad, S., Dai, W., Wang, H., Lu, S., Nandre, R., Gaur, P., Lopez, J., Sade-Feldman, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0441-y · Cited by 333 · see citing works
Self-citationChalabi, M., Cardona, A., Nagarkar, D. R., Dhawahir Scala, A., Gandara, D. R., Rittmeyer, A., Albert, M. L., Powles, T., Kok, M., & Herrera, F. G. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.01.006 · Cited by 294 · see citing works
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Self-citationLearning from clinical trials of neoadjuvant checkpoint blockade
Versluis, J. M., Long, G. V., & Blank, C. U. (2020) · Nature Medicine · doi:10.1038/s41591-020-0829-0 · Cited by 234 · see citing works
Yang, S., Tang, Z., Hu, C., Zhang, D., Shen, N., Yu, H., & Chen, X. (2019) · Advanced Materials · doi:10.1002/adma.201805955 · Cited by 210 · see citing works
Fumet, J.-D., Richard, C., Ledys, F., Klopfenstein, Q., Joubert, P., Routy, B., Truntzer, C., Gagné, A., Hamel, M.-A., Guimaraes, C. F., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0220-9 · Cited by 176 · see citing works
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Chuckran, C. A., Liu, C., Bruno, T. C., Workman, C. J., & Vignali, D. A. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000967 · Cited by 147 · see citing works
Zappasodi, R., Budhu, S., Hellmann, M. D., Postow, M. A., Senbabaoglu, Y., Manne, S., Gasmi, B., Liu, C., Zhong, H., Li, Y., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.009 · Cited by 142 · see citing works
Self-citationPai, C.-C. S., Huang, J. T., Lu, X., Simons, D. M., Park, C., Chang, A., Tamaki, W., Liu, E., Roybal, K. T., Seagal, J., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.006 · Cited by 141 · see citing works
Gainor, J. F., Patel, M. R., Weber, J. S., Gutierrez, M., Bauman, J. E., Clarke, J. M., Julian, R., Scott, A. J., Geiger, J. L., Kirtane, K., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0158 · Cited by 124 · see citing works
Buchan, S. L., Fallatah, M., Thirdborough, S. M., Taraban, V. Y., Rogel, A., Thomas, L. J., Penfold, C. A., He, L.-Z., Curran, M. A., Keler, T., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3057 · Cited by 114 · see citing works
Yu, J., Yan, J., Guo, Q., Chi, Z., Tang, B., Zheng, B., Yu, J., Yin, T., Cheng, Z., Wu, X., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0475 · Cited by 100 · see citing works
Luo, R., Firat, E., Gaedicke, S., Guffart, E., Watanabe, T., & Niedermann, G. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1344 · Cited by 91 · see citing works
Phase Ib/II Study of Pembrolizumab and Pegylated-Interferon Alfa-2b in Advanced Melanoma
Davar, D., Wang, H., Chauvin, J.-M., Pagliano, O., Fourcade, J. J., Ka, M., Menna, C., Rose, A., Sander, C., Borhani, A. A., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.18.00632 · Cited by 86 · see citing works
Nam, G.-H., Kwon, M., Jung, H., Ko, E., Kim, S. A., Choi, Y., Song, S. J., Kim, S., Lee, Y., Kim, G. B., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002474 · Cited by 82 · see citing works
Goubet, A.-G., Lordello, L., Alves Costa Silva, C., Peguillet, I., Gazzano, M., Mbogning-Fonkou, M. D., Thelemaque, C., Lebacle, C., Thibault, C., Audenet, F., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0201 · Cited by 86 · see citing works
Perspectives on the Neoadjuvant Use of Immunotherapy in Hepatocellular Carcinoma
Pinato, D. J., Fessas, P., Sapisochin, G., & Marron, T. U. (2021) · Hepatology · doi:10.1002/hep.31697 · Cited by 74 · see citing works
Anti-PD-1 Therapy Response Predicted by the Combination of Exosomal PD-L1 and CD28
Zhang, C., Fan, Y., Che, X., Zhang, M., Li, Z., Li, C., Wang, S., Wen, T., Hou, K., Shao, X., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00760 · Cited by 69 · see citing works
Peng, H., James, C. A., Cullinan, D. R., Hogg, G. D., Mudd, J. L., Zuo, C., Takchi, R., Caldwell, K. E., Liu, J., DeNardo, D. G., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0998 · Cited by 61 · see citing works
de Goeje, P. L., Poncin, M., Bezemer, K., Kaijen-Lambers, M. E. H., Groen, H. J. M., Smit, E. F., Dingemans, A.-M. C., Kunert, A., Hendriks, R. W., & Aerts, J. G. J. V. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2243 · Cited by 43 · see citing works
Mankor, J. M., Disselhorst, M. J., Poncin, M., Baas, P., Aerts, J. G. J. V., & Vroman, H. (2020) · eBioMedicine · doi:10.1016/j.ebiom.2020.103040 · Cited by 45 · see citing works
Network approach in liquidomics landscape
Santini, D., Botticelli, A., Galvano, A., Iuliani, M., Incorvaia, L., Gristina, V., Taffon, C., Foderaro, S., Paccagnella, E., Simonetti, S., et al. (2023) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-023-02743-9 · Cited by 37 · see citing works
Pirozyan, M. R., McGuire, H. M., Emran, A. A., Tseng, H.-Y., Tiffen, J. C., Lee, J. H., Carlino, M. S., Menzies, A. M., Long, G. V., Scolyer, R. A., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00372 · Cited by 34 · see citing works
Castello, A., Rossi, S., Toschi, L., & Lopci, E. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10061251 · Cited by 36 · see citing works
Sekido, K., Tomihara, K., Tachinami, H., Heshiki, W., Sakurai, K., Moniruzzaman, R., Imaue, S., Fujiwara, K., & Noguchi, M. (2019) · Oral Oncology · doi:10.1016/j.oraloncology.2019.104462 · Cited by 23 · see citing works
From mucosal infection to successful cancer immunotherapy
Goubet, A.-G., Rouanne, M., Derosa, L., Kroemer, G., & Zitvogel, L. (2023) · Nature Reviews Urology · doi:10.1038/s41585-023-00784-5 · Cited by 11 · see citing works
Barber, E. L., Chen, S., Pineda, M. J., Robertson, S. E., Hill, E. K., Teoh, D., Schilder, J., O'Shea, K. L., Kocherginsky, M., Zhang, B., et al. (2022) · Cancer Research Communications · doi:10.1158/2767-9764.crc-22-0147 · Cited by 9 · see citing works
- Authors
- Huang, A. C., Postow, M. A., Orlowski, R. J., Mick, R., Bengsch, B., Manne, S., Xu, W., Harmon, S., Giles, J. R., Wenz, B., Adamow, M., Kuk, D., Panageas, K. S., Carrera, C., Wong, P., Quagliarello, F., Wubbenhorst, B., D’Andrea, K., Pauken, K. E., Herati, R. S., Staupe, R. P., Schenkel, J. M., McGettigan, S., Kothari, S., George, S. M., Vonderheide, R. H., Amaravadi, R. K., Karakousis, G. C., Schuchter, L. M., Xu, X., Nathanson, K. L., Wolchok, J. D., Gangadhar, T. C., & Wherry, E. J.
- Affiliations
- Parker Institute for Cancer Immunotherapy (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Pennsylvania (US)
- Abramson Cancer Center (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Huang, Alexander C.
- Gangadhar, Tara C.
- Wherry, E. John
- ORCID
- Huang, Alexander C.
- Postow, Michael A.
- Orlowski, Robert J.
- Mick, Rosemarie
- Bengsch, Bertram
- Manne, Sasikanth
- Xu, Wei
- Giles, Josephine R.
- Adamow, Matthew
- Kuk, Deborah
- Panageas, Katherine S.
- Carrera, Cristina
- Wong, Phillip
- Wubbenhorst, Bradley
- Pauken, Kristen E.
- Herati, Ramin S.
- Staupe, Ryan P.
- Schenkel, Jason M.
- McGettigan, Suzanne
- Vonderheide, Robert H.
- Amaravadi, Ravi K.
- Karakousis, Giorgos C.
- Schuchter, Lynn M.
- Xu, Xiaowei
- Nathanson, Katherine L.
- Wolchok, Jedd D.
- Wherry, E. John
- Venue
- Nature
- Published
- 2017-04-10
- Volume
- 545
- Issue
- 7652
- Pages
- 60-65
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5554367
- OpenAlex
- W2605630275
- Cited by
- 1,664
- References
- 34
- Citations by year
- 2026: 105 · 2025: 132 · 2024: 158 · 2023: 187 · 2022: 207 · 2021: 231 · 2020: 228 · 2019: 203 · 2018: 165 · 2017: 46
- FWCI
- 77.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- National Institutes of Health (KL2TR001879)
- National Institute on Aging (F32AG047773)
- National Cancer Institute (T32CA009140, P01CA114046, P50CA174523, P30CA008748, T32CA009615, P30CA016520)
- National Institute of Allergy and Infectious Diseases (R01AI105343, K08AI114852, U19AI117950, U19AI082630, P01AI108545)
- National Center for Advancing Translational Sciences
- 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, pembrolizumab, advanced melanoma, exhausted CD8+ T cells, T cell reinvigoration, tumor burden, peripheral blood T cells, immune checkpoint inhibitors, predictive biomarkers, treatment response prediction, pharmacodynamics
- MeSH terms
- Female, Humans, Male, Melanoma, Neoplasm Staging, Phenotype, Treatment Outcome, CD8-Positive T-Lymphocytes, Ki-67 Antigen, Tumor Burden, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized
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