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J Hematol Oncol. 2016 May 27;9(1):47. doi: 10.1186/s13045-016-0277-y.

Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy.

Ma W1,2, Gilligan BM1, Yuan J3,4, Li T5,6.

Author information

1
Division of Hematology & Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, University of California, Davis, School of Medicine, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA.
2
Former visiting medical student from School of Medicine, Peking University Health Science Center, No. 38 Xueyuan Road, Beijing, 100191, China.
3
Immune Monitoring Core, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 386, New York, NY10065, USA.
4
Present address: Oncology Clinical Research, Merck Research Laboratories, Rahway, NJ07065, USA.
5
Division of Hematology & Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, University of California, Davis, School of Medicine, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA. thli@ucdavis.edu.
6
VA Northern California Health Care System, 10535 Hospital Way, Mather, CA, 95655, USA. thli@ucdavis.edu.

Abstract

Modulating immune inhibitory pathways has been a major recent breakthrough in cancer treatment. Checkpoint blockade antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programed cell-death protein 1 (PD-1) have demonstrated acceptable toxicity, promising clinical responses, durable disease control, and improved survival in some patients with advanced melanoma, non-small cell lung cancer (NSCLC), and other tumor types. About 20 % of advanced NSCLC patients and 30 % of advanced melanoma patients experience tumor responses from checkpoint blockade monotherapy, with better clinical responses seen with the combination of anti-PD-1 and anti-CTLA-4 antibodies. Given the power of these new therapies, it is important to understand the complex and dynamic nature of host immune responses and the regulation of additional molecules in the tumor microenvironment and normal organs in response to the checkpoint blockade therapies. In this era of precision oncology, there remains a largely unmet need to identify the patients who are most likely to benefit from immunotherapy, to optimize the monitoring assays for tumor-specific immune responses, to develop strategies to improve clinical efficacy, and to identify biomarkers so that immune-related adverse events can be avoided. At this time, PD-L1 immunohistochemistry (IHC) staining using 22C3 antibody is the only FDA-approved companion diagnostic for patients with NSCLC-treated pembrolizumab, but more are expected to come to market. We here summarize the current knowledge, clinical efficacy, potential immune biomarkers, and associated assays for immune checkpoint blockade therapies in advanced solid tumors.

KEYWORDS:

Biomarker; Cancer immunotherapy; Cytotoxic T cells; Immune checkpoint blockade antibodies; Immune-related adverse events; PD-1; PD-L1; Precision oncology

PMID:
27234522
PMCID:
PMC4884396
DOI:
10.1186/s13045-016-0277-y
[Indexed for MEDLINE]
Free PMC Article

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