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Cancer Immunol Res. 2016 Mar;4(3):194-203. doi: 10.1158/2326-6066.CIR-15-0210. Epub 2016 Jan 19.

PD-1 Blockade Expands Intratumoral Memory T Cells.

Author information

1
Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California. Division of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, Los Angeles, California. bcomin@mednet.ucla.edu aribas@mednet.ucla.edu.
2
Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
3
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
4
Departments of Biological Sciences and Systems Biology, Columbia University, New York, New York.
5
CytoAnalysis, Denver, Colorado.
6
Department of General Internal Medicine and Healthy Services Research, University of California Los Angeles, Los Angeles, California.
7
Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, Los Angeles, California. Department of Medicine, Division of Dermatology. University of California Los Angeles, Los Angeles, California.
8
Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York.
9
Division of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, Los Angeles, California. bcomin@mednet.ucla.edu aribas@mednet.ucla.edu.

Abstract

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.

PMID:
26787823
PMCID:
PMC4775381
[Available on 2017-03-01]
DOI:
10.1158/2326-6066.CIR-15-0210
[Indexed for MEDLINE]
Free PMC Article

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