Journal
CANCER IMMUNOLOGY RESEARCH
Volume 4, Issue 3, Pages 194-203Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-15-0210
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Funding
- NIH [R35 CA197633, P01 CA168585, CA16042, AI 28697]
- Stand Up To Cancer - Cancer Research Institute (SU2C-CRI) Cancer Immunology Dream Team Translational Research Grant [SU2C-AACR-DT1012]
- Stand Up To Cancer Phillip A. Sharp Innovation in Collaboration Award [SU2C-AACR-PS04]
- Oncology training grant [5T32CA009297-30]
- Dermatology training grant [5T32AR058921-05]
- Tumor Immunology training grant [5T32CA009120-39]
- Tower Cancer Research Foundation Grant
- JCCC
- UCLA AIDS Institute
- David Geffen School of Medicine at UCLA
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Tumor responses to programmed cell death protein 1 (PD-1) blockade therapy are mediated by T cells, which we characterized in 102 tumor biopsies obtained from 53 patients treated with pembrolizumab, an antibody to PD-1. Biopsies were dissociated, and single-cell infiltrates were analyzed by multicolor flow cytometry using two computational approaches to resolve the leukocyte phenotypes at the single-cell level. There was a statistically significant increase in the frequency of T cells in patients who responded to therapy. The frequency of intratumoral B cells and monocytic myeloid-derived suppressor cells significantly increased in patients' biopsies taken on treatment. The percentage of cells with a regulatory T-cell phenotype, monocytes, and natural killer cells did not change while on PD-1 blockade therapy. CD8(+) memory T cells were the most prominent phenotype that expanded intratumorally on therapy. However, the frequency of CD4(+) effector memory T cells significantly decreased on treatment, whereas CD4(+) effector T cells significantly increased in nonresponding tumors on therapy. In peripheral blood, an unusual population of blood cells expressing CD56 was detected in two patients with regressing melanoma. In conclusion, PD-1 blockade increases the frequency of T cells, B cells, and myeloid-derived suppressor cells in tumors, with the CD8(+) effector memory T-cell subset being the major T-cell phenotype expanded in patients with a response to therapy. (C) 2016 AACR.
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