PD-L1 expression as a predictive biomarker in cancer immunotherapy

Patel, Sandip Pravin; Kurzrock, Razelle

doi:10.1158/1535-7163.mct-14-0983

Cited by 2,291Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

PD-L1 expression as a predictive biomarker in cancer immunotherapy

Patel, Sandip Pravin, Kurzrock, Razelle·2015·Molecular Cancer Therapeutics

DOI 10.1158/1535-7163.mct-14-0983

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Abstract

The resurgence of cancer immunotherapy stems from an improved understanding of the tumor microenvironment. The PD-1/PD-L1 axis is of particular interest, in light of promising data demonstrating a restoration of host immunity against tumors, with the prospect of durable remissions. Indeed, remarkable clinical responses have been seen in several different malignancies including, but not limited to, melanoma, lung, kidney, and bladder cancers. Even so, determining which patients derive benefit from PD-1/PD-L1-directed immunotherapy remains an important clinical question, particularly in light of the autoimmune toxicity of these agents. The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells. Emerging data suggest that patients whose tumors overexpress PD-L1 by IHC have improved clinical outcomes with anti-PD-1-directed therapy, but the presence of robust responses in some patients with low levels of expression of these markers complicates the issue of PD-L1 as an exclusionary predictive biomarker. An improved understanding of the host immune system and tumor microenvironment will better elucidate which patients derive benefit from these promising agents.

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Limited biomarkers such as PD-L1 expression and tumor mutation load are clinically used to predict immunotherapy benefit.
“Currently, limited biomarkers, such as PD-L1 expression (88) and tumor mutation load (TMB) (89–91), are clinically used to predict the immunotherapy benefit.”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [88]

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Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment
D’Angelo, S. P., Shoushtari, A. N., Agaram, N. P., Kuk, D., Qin, L., Carvajal, R. D., Dickson, M. A., Gounder, M. M., Keohan, M. L., Schwartz, G. K., et al. (2014) · Human Pathology · doi:10.1016/j.humpath.2014.11.001 · Cited by 300 · see citing works
PTEN Loss Increases PD-L1 Protein Expression and Affects the Correlation between PD-L1 Expression and Clinical Parameters in Colorectal Cancer
Song, M., Chen, D., Lu, B., Wang, C., Zhang, J., Huang, L., Wang, X., Timmons, C. L., Hu, J., Liu, B., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065821 · Cited by 266 · see citing works
Tumor-Expressed B7-H1 and B7-DC in Relation to PD-1+ T-Cell Infiltration and Survival of Patients with Cervical Carcinoma
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 250 · see citing works
Cancer immunotherapy: The past, the present and the future
Parish, C. R. (2003) · Immunology and Cell Biology · doi:10.1046/j.0818-9641.2003.01151.x · Cited by 240 · see citing works
Abstract 2859: Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC)
Emens, L. A., Braiteh, F. S., Cassier, P. A., Delord, J., Eder, J. P., Fassò, M., Xiao, Y., Wang, Y., Molinero, L. L., Chen, D. S., et al. (2015) · Cancer Research · doi:10.1158/1538-7445.am2015-2859 · Cited by 211 · see citing works
A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors.
Herbst, R. S., Gordon, M. S., Fine, G. D., Sosman, J. A., Soria, J., Hamid, O., Powderly, J. D., Burris, H. A., Mokatrin, A., Kowanetz, M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.3000 · Cited by 191 · see citing works
Exploiting CTLA-4, PD-1 and PD-L1 to reactivate the host immune response against cancer
Quezada, S. A., & Peggs, K. S. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.117 · Cited by 189 · see citing works
Costimulatory molecule B7‐H1 in primary and metastatic clear cell renal cell carcinoma
Thompson, R. H., Gillett, M. D., Cheville, J. C., Lohse, C. M., Dong, H., Webster, W. S., Chen, L., Zincke, H., Blute, M. L., Leibovich, B. C., et al. (2005) · Cancer · doi:10.1002/cncr.21470 · Cited by 174 · see citing works
Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Grosso, J. F., Horak, C. E., Inzunza, H. D., Cardona, D. M., Simon, J. S., Gupta, A. K., Sankar, V., Park, J.-S., Kollia, G. D., Taube, J. M., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.3016 · Cited by 158 · see citing works
Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations
Tougeron, D., Fauquembergue, É., Rouquette, A., Pessot, F. L., Sesboüé, R., Laurent, M., Berthet, P., Mauillon, J., Fiore, F. D., Sabourin, J., et al. (2009) · Modern Pathology · doi:10.1038/modpathol.2009.80 · Cited by 153 · see citing works
Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).
Sznol, M., Kluger, H. M., Callahan, M. K., Postow, M. A., Gordon, R. A., Segal, N. H., Rizvi, N. A., Lesokhin, A. M., Atkins, M. B., Kirkwood, J. M., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.lba9003 · Cited by 151 · see citing works
Adjuvant Chemotherapy With Sequential or Concurrent Anthracycline and Docetaxel: Breast International Group 02 98 Randomized Trial
Francis, P. A., Crown, J. P., Leo, A. D., Buyse, M. E., Balil, A., Andersson, M., Nordenskjöld, B. A., Láng, I., Jakesz, R., Vorobiof, D., et al. (2008) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm287 · Cited by 150 · see citing works
Clinical significance of B7-H1（PD-L1）expression in human acute leukemia
Chen, X., Liu, S., Wang, L., Zhang, W., Ji, Y., & Ma, X. (2008) · Cancer Biology & Therapy · doi:10.4161/cbt.7.5.5689 · Cited by 122 · see citing works
Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial.
Hodi, F. S., Sznol, M., Kluger, H. M., McDermott, D. F., Carvajal, R. D., Lawrence, D. P., Topalian, S. L., Atkins, M. B., Powderly, J. D., Sharfman, W. H., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.9002 · Cited by 118 · see citing works
Abstract S1-09: A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer
Nanda, R., Chow, L. Q. M., Dees, E. C., Berger, R., Gupta, S., Geva, R., Pusztai, L., Dolled-Filhart, M. P., Emancipator, K., Gonzalez, E. J., et al. (2015) · Cancer Research · doi:10.1158/1538-7445.sabcs14-s1-09 · Cited by 114 · see citing works
First-line nivolumab (anti-PD-1; BMS-936558, ONO-4538) monotherapy in advanced NSCLC: Safety, efficacy, and correlation of outcomes with PD-L1 status.
Gettinger, S. N., Shepherd, F. A., Antonia, S. J., Brahmer, J. R., Chow, L. Q. M., Juergens, R. A., Borghaei, H., Shen, Y., Harbison, C. T., Alaparthy, S., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.8024 · Cited by 104 · see citing works
Inhibition of PD-L1 by MPDL3280A and clinical activity in pts with metastatic urothelial bladder cancer (UBC).
Powles, T. B., Vogelzang, N. J., Fine, G. D., Eder, J. P., Braiteh, F. S., Loriot, Y., Cruz, C., Joaquim Bellmunt, B., Burris, H. A., Teng, S.-L. M., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.5011 · Cited by 96 · see citing works
Clinical efficacy and correlation with tumor PD-L1 expression in patients (pts) with melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475.
Kefford, R. F., Ribas, A., Hamid, O., Robert, C., DAUD, A. I., Wolchok, J. D., Joshua, A. M., Hodi, F. S., Gangadhar, T. C., Hersey, P., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.3005 · Cited by 89 · see citing works
The Future of Cancer Therapy: Selecting Patients Likely to Respond to PD1/L1 Blockade
Ribas, A., & Tumeh, P. C. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0933 · Cited by 88 · see citing works
Abstract CT105: MK-3475 (anti-PD-1 monoclonal antibody) for non-small cell lung cancer (NSCLC): Antitumor activity and association with tumor PD-L1 expression
Gandhi, L., Balmanoukian, A. S., Hui, R., Hamid, O., Rizvi, N. A., Leighl, N. B., Gubens, M. A., Goldman, J. W., Lubiniecki, G. M., Emancipator, K., et al. (2014) · Cancer Research · doi:10.1158/1538-7445.am2014-ct105 · Cited by 55 · see citing works
The role of leukemia-derived B7-H1 (PD-L1) in tumor–T-cell interactions in humans
Salih, H. R., Wintterle, S., Krusch, M., Kroner, A., Huang, Y.-H., Chen, L., & Wiendl, H. (2006) · Experimental Hematology · doi:10.1016/j.exphem.2006.03.006 · Cited by 49 · see citing works
Tumor infiltrating lymphocytes (TILs) indicate trastuzumab benefit in early-stage HER2-positive breast cancer (HER2+ BC)
Loi, S., Michiels, S., Salgado, R., Sirtaine, N., José, V., Fumagalli, D., Brown, D. N., Kellokumpu‐Lehtinen, P., Bono, P., Kataja, V. V., et al. (2013) · Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) · Cited by 36 · see citing works
Abstract S1-05: Tumor infiltrating lymphocytes (TILs) indicate trastuzumab benefit in early-stage HER2-positive breast cancer (HER2+ BC)
Loi, S., Michiels, S., Salgado, R., Sirtaine, N., José, V., Fumagalli, D., Brown, D., Kellokumpu-Lehtinen, P.-L., Bono, P., Kataja, V. V., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.sabcs13-s1-05 · Cited by 33 · see citing works
Peripheral and tumor immune correlates in patients with advanced melanoma treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) monotherapy or in combination with ipilimumab
Postow, M. A., Cardona, D. M., Taube, J. M., Anders, R. A., Taylor, C. R., Wolchok, J. D., Callahan, M. K., Curran, M. A., Lesokhin, A. M., Grosso, J. F., et al. (2014) · Journal of Translational Medicine · doi:10.1186/1479-5876-12-s1-o8 · Cited by 29 · see citing works
Programmed death-ligand 1 (PD-L1) expression in various tumor types
Grosso, J. F., Inzunza, H. D., Wu, Q., Simon, J. S., Singh, P., Zhang, X., Phillips, T., Simmons, P., & Cogswell, J. P. (2013) · Journal for ImmunoTherapy of Cancer · doi:10.1186/2051-1426-1-s1-p53 · Cited by 29 · see citing works
PD-L1 expression in primary clear cell renal cell carcinomas (ccRCCs) and their metastases.
Callea, M., Genega, E. M., Gupta, M., Fay, A. P., Song, J., Carvo, I., Bhatt, R. S., McDermott, D. F., Atkins, M. B., Choueiri, T. K., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.4_suppl.467 · Cited by 29 · see citing works
Concordance of PD-L1 expression by different immunohistochemistry (IHC) definitions and in situ hybridization (ISH) in squamous cell carcinoma (SCC) of the lung.
Martínez‐Martí, A., Martínez, P., Navarro, A., Cedrés, S., Murtra-Garrell, N., Salvà, F., Sansano, I., Laura, R. V., Felip, E., & Nuciforo, P. G. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.7569 · Cited by 18 · see citing works
Programmed death 1 (PD-1) lymphocytes and ligand (PD-L1) in colorectal cancer and their relationship to microsatellite instability status.
Gatalica, Z., Snyder, C., Yeatts, K. A., Xiao, N., Holterman, D. A., & Lynch, H. T. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.3625 · Cited by 18 · see citing works
PD-L1 expression and survival in patients with non-small cell lung cancer (NSCLC) in Korea.
Sun, J., Zhou, W., Choi, Y., Choi, S., Kim, S. E., Wang, Z., Dolled-Filhart, M. P., Emancipator, K., WEINER, R. S., Park, M., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.8066 · Cited by 16 · see citing works
Modulation of Immune System Inhibitory Checkpoints in Colorectal Cancer
Patel, S. P., Osada, T., Osada, K., Hurwitz, H. I., Lyerly, H. K., & Morse, M. A. (2013) · Current Colorectal Cancer Reports · doi:10.1007/s11888-013-0184-3 · Cited by 9 · see citing works
Self-citation
Correlation of PDL1 tumor expression and outcomes in renal cell carcinoma (RCC) patients (pts) treated with pazopanib (paz).
Figueroa, D. J., Liu, Y., Gagnon, R., Carpenter, C. L., Dar, M. M., & Bartlett-Pandite, A. N. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.31.15_suppl.3021 · Cited by 6 · see citing works
PD-L1 expression in non-clear cell renal cell carcinoma and benign kidney tumors.
Fay, A. P., Callea, M., Gray, K. P., Ho, T. H., Song, J., Carvo, I., Lampron, M. E., Albiges, L. K., Stanton, M., McDermott, D. F., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.4526 · Cited by 6 · see citing works
Validation of Elevated Blood Soluble PD-L1 As an Independent Prognostic Marker in Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)
Fest, T., Cerhan, J. R., Gandhi, M. K., Azzaoui, I., Crooks, P., Maurer, M. J., Milpied, N. J., Hertzberg, M., Lamy, T., Ansell, S. M., et al. (2014) · Blood · doi:10.1182/blood.v124.21.2998.2998 · Cited by 5 · see citing works
PD-L1 expression in mononuclear cells and not in tumor cells, correlated with prognosis in metastatic urothelial carcinoma.
Mullane, S. A., Werner, L. L., Callea, M., Fay, A. P., Leow, J. J. J., Choueiri, T. K., Freeman, G. J., Signoretti, S., Hodi, F. S., & Joaquim Bellmunt, B. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.4552 · Cited by 5 · see citing works
PD1 and PD-L1 expression in glioblastoma.
Berghoff, A. S., Kiesel, B., Widhalm, G., Rajky, O., Ricken, G., Wöehrer, A., Dieckmann, K. U., Filipits, M., Zielinski, C. C., Marosi, C., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.2011 · Cited by 5 · see citing works
PD-L1 expression and immune infiltrates in sarcoma.
D’Angelo, S. P., Shoushtari, A. N., Agaram, N. P., Kuk, D., Qin, L., Carvajal, R. D., Dickson, M. A., Gounder, M. M., Keohan, M. L., Schwartz, G. K., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.10522 · Cited by 5 · see citing works
Expression of PD-L1 and NY-ESO-1 in early and advanced triple-negative breast cancer.
Tessari, A., Paolini, B., Mariani, L., Pilla, L., Carcangiu, M. L., Moliterni, A., de Braud, F., & Cresta, S. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.1110 · Cited by 3 · see citing works
Programmed death receptor ligand-1 (PD-L1) expression in a thymoma (T) tissue microarray (TMA).
Padda, S. K., Riess, J. W., Schwartz, E., Tian, L., Kohrt, H. E. K., Neal, J. W., Natkunam, Y., West, R. B., & Wakelee, H. A. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.32.15_suppl.7606 · Cited by 2 · 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
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition
Buchbinder, E. I., & Desai, A. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000239 · Cited by 2,360 · see citing works
Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers
Goodman, A. M., Kato, S., Bazhenova, L., Patel, S. P., Frampton, G. M., Miller, V., Stephens, P. J., Daniels, G. A., & Kurzrock, R. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0386 · Cited by 2,264 · see citing works
Self-citation
Non–Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment
Duma, N., Santana-Dávila, R., & Molina, J. R. (2019) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.01.013 · Cited by 2,218 · see citing works
Immune checkpoint inhibitors: recent progress and potential biomarkers
Darvin, P., Toor, S. M., Sasidharan Nair, V., & Elkord, E. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0191-1 · Cited by 2,035 · see citing works
Molecular therapies and precision medicine for hepatocellular carcinoma
Llovet, J. M., Montal, R., Sia, D., & Finn, R. S. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0073-4 · Cited by 1,948 · see citing works
Predictive biomarkers for checkpoint inhibitor-based immunotherapy
Gibney, G. T., Weiner, L. M., & Atkins, M. B. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30406-5 · Cited by 1,635 · see citing works
Neuroinflammation and Central Sensitization in Chronic and Widespread Pain
Ji, R.-R., Nackley, A., Huh, Y., Terrando, N., & Maixner, W. (2018) · Anesthesiology · doi:10.1097/aln.0000000000002130 · Cited by 1,630 · see citing works
Current state of immunotherapy for glioblastoma
Lim, M. K., Xia, Y., Bettegowda, C., & Weller, M. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0003-5 · Cited by 1,373 · see citing works
Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors
Galluzzi, L., Humeau, J., Buqué, A., Zitvogel, L., & Kroemer, G. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0413-z · Cited by 1,349 · see citing works
PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project
Hirsch, F. R., McElhinny, A., Stanforth, D., Ranger‐Moore, J., Jansson, M., Kulangara, K., Richardson, W., Towne, P., Hanks, D. A., Vennapusa, B., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.11.2228 · Cited by 1,277 · see citing works
Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial
Kaufman, H. L., Russell, J., Hamid, O., Bhatia, S., Terheyden, P., D'Angelo, S. P., Shih, K. C., Lebbé, C., Linette, G. P., Milella, M., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30364-3 · Cited by 1,236 · see citing works
The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker
Jardim, D. L., Goodman, A., de Melo Gagliato, D., & Kurzrock, R. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.10.001 · Cited by 1,192 · see citing works
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A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging
Keren, L., Bosse, M., Marquez, D., Angoshtari, R., Jain, S., Varma, S., Yang, S.-R., Kurian, A., Van Valen, D., West, R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.039 · Cited by 1,183 · see citing works
Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling
Chaudhuri, A. A., Chabon, J. J., Lovejoy, A. F., Newman, A. M., Stehr, H., Azad, T. D., Khodadoust, M. S., Esfahani, M. S., Liu, C. L., Zhou, L., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0716 · Cited by 1,091 · see citing works
Targeting neoantigens to augment antitumour immunity
Yarchoan, M., Johnson, B. A., Lutz, E. R., Laheru, D. A., & Jaffee, E. M. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.154 · Cited by 997 · see citing works
The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors
Davis, A. A., & Patel, V. G. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0768-9 · Cited by 960 · see citing works
Molecular profiling for precision cancer therapies
Malone, E. R., Oliva, M., Sabatini, P. J. B., Stockley, T. L., & Siu, L. L. (2020) · Genome Medicine · doi:10.1186/s13073-019-0703-1 · Cited by 942 · see citing works
Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer
Derosa, L., Hellmann, M. D., Spaziano, M., Halpenny, D., Fidelle, M., Rizvi, H., Long, N., Plodkowski, A. J., Arbour, K. C., Chaft, J. E., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy103 · Cited by 908 · see citing works
Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study
Powles, T., O'Donnell, P. H., Massard, C., Arkenau, H.-T., Friedlander, T. W., Hoimes, C. J., Lee, J. L., Ong, M., Sridhar, S. S., Vogelzang, N. J., et al. (2017) · JAMA Oncology · doi:10.1001/jamaoncol.2017.2411 · Cited by 869 · see citing works
Integrative clinical genomics of metastatic cancer
Robinson, D. R., Wu, Y.-M., Lonigro, R. J., Vats, P., Cobain, E., Everett, J., Cao, X., Rabban, E., Kumar-Sinha, C., Raymond, V., et al. (2017) · Nature · doi:10.1038/nature23306 · Cited by 863 · see citing works
Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study
Matulonis, U. A., Shapira‐Frommer, R., Santin, A. D., Lisyanskaya, A. S., Pignata, S., Vergote, I. B., Raspagliesi, F., Sonke, G. S., Birrer, M. J., Provencher, D. M., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz135 · Cited by 855 · see citing works
Hyperprogressors after Immunotherapy: Analysis of Genomic Alterations Associated with Accelerated Growth Rate
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Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study
Adams, S., Schmid, P., Rugo, H. S., Winer, E. P., Loirat, D., Awada, A., Cescon, D. W., Iwata, H., Campone, M., Nanda, R., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdy517 · Cited by 807 · see citing works
Review of precision cancer medicine: Evolution of the treatment paradigm
Tsimberidou, A. M., Fountzilas, E., Nikanjam, M., & Kurzrock, R. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102019 · Cited by 776 · see citing works
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Tumor biomarkers for diagnosis, prognosis and targeted therapy
Zhou, Y., Tao, L., Qiu, J., Xu, J., Yang, X., Zhang, Y., Tian, X., Guan, X., Cen, X., & Zhao, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01823-2 · Cited by 772 · see citing works
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells
Rupp, L. J., Schumann, K., Roybal, K. T., Gate, R. E., Ye, C. J., Lim, W. A., & Marson, A. (2017) · Scientific Reports · doi:10.1038/s41598-017-00462-8 · Cited by 757 · see citing works
Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study
Dirix, L. Y., Takács, I., Jérusalem, G., Nikolinakos, P. G., Arkenau, H., Forero, A., Boccia, R. V., Lippman, M. E., Somer, R. A., Šmakal, M., et al. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4537-5 · Cited by 748 · see citing works
Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study
Sicklick, J. K., Kato, S., Okamura, R., Schwaederle, M. C., Hahn, M. E., Williams, C. B., De, P. K., Krie, A. K., Piccioni, D. E., Miller, V. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0407-5 · Cited by 713 · see citing works
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Integrating oncolytic viruses in combination cancer immunotherapy
Bommareddy, P. K., Shettigar, M., & Kaufman, H. L. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0014-6 · Cited by 704 · see citing works
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Authors: Patel, S. P., & Kurzrock, R.
Affiliations: University of California San Diego (US)
ORCID: Patel, Sandip Pravin
Kurzrock, Razelle
Venue: Molecular Cancer Therapeutics
Publisher: American Association for Cancer Research (AACR)
Published: 2015-04-01
Volume: 14
Issue: 4
Pages: 847-856
ISSN: 1535-7163 (ISSN-L)
1538-8514
DOI: 10.1158/1535-7163.mct-14-0983
OpenAlex: W2136859769
Cited by: 2,291
References: 112
Citations by year: 2026: 76 · 2025: 156 · 2024: 231 · 2023: 261 · 2022: 278 · 2021: 318 · 2020: 282 · 2019: 202 · 2018: 189 · 2017: 157 · 2016: 110 · 2015: 27
FWCI: 17.32
Type: journal article
Language: en
Open access: closed
Locations: Molecular Cancer Therapeutics (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: PD-L1, predictive biomarkers, cancer immunotherapy, PD-1/PD-L1 axis, tumor microenvironment, immunohistochemistry, anti-PD-1 therapy, immune checkpoint inhibitors, autoimmune toxicity, tumor-infiltrating immune cells, melanoma, lung cancer, kidney cancer, bladder cancer
MeSH terms: Animals, Humans, Immunohistochemistry, Immunotherapy, Neoplasms, Phenotype, Prognosis, Biomarkers, Gene Expression, Immunophenotyping, B7-H1 Antigen

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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PD-L1 expression as a predictive biomarker in cancer immunotherapy

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