期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 67, 期 11, 页码 1767-1776出版社
SPRINGER
DOI: 10.1007/s00262-018-2228-7
关键词
PD-1; Immunotherapy; CD8 T cells; T cell repertoire; Melanoma
资金
- Winship Cancer Institute Melanoma Research Pilot Grant
- Emory University School of Medicine Flow Cytometry Core
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005034, ZIAAI005066, ZIAAI005033, P01AI080192] Funding Source: NIH RePORTER
PD-1-targeted therapy has dramatically changed advanced cancer treatment. However, many questions remain, including specificity of T cells activated by PD-1 therapy and how peripheral blood analysis correlates to effects at tumor sites. In this study, we utilized TCR sequencing to dissect the composition of peripheral blood CD8 T cells activated upon therapy, comparing it with tumor-infiltrating lymphocytes. We report on a nonagenarian melanoma patient who showed a prominent increase in peripheral blood Ki-67+CD8 T cells following brain stereotactic radiation and anti-PD-1 immunotherapy. Proliferating CD8 T cells exhibited an effector-like phenotype with expression of CD38, HLA-DR and Granzyme B, as well as expression of the positive costimulatory molecules CD28 and CD27. TCR sequencing of peripheral blood CD8 T cells revealed a highly oligoclonal repertoire at baseline with one clonotype accounting for 30%. However, the majority of dominant clonesincluding a previously identified cytomegalovirus-reactive clonedid not expand following treatment. In contrast, expanding clones were present at low frequencies in the peripheral blood but were enriched in a previously resected liver metastasis. The patient has so far remained recurrence-free for 36 months, and several CD8 T cell clones that expanded after treatment were maintained at elevated levels for at least 8 months. Our data show that even in a nonagenarian individual with oligoclonal expansion of CD8 T cells, we can identify activation of tumor-infiltrating CD8 T cell clones in peripheral blood following anti-PD-1-based immunotherapies.
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