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- Title
Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8<sup>+</sup> T cells.
- Authors
Mizukoshi, Eishiro; Nakagawa, Hidetoshi; Tamai, Toshikatsu; Kitahara, Masaaki; Fushimi, Kazumi; Nio, Kouki; Terashima, Takeshi; Iida, Noriho; Arai, Kuniaki; Yamashita, Tatsuya; Yamashita, Taro; Sakai, Yoshio; Honda, Masao; Kaneko, Shuichi
- Abstract
The behaviors and fates of immune cells in cancer patients, such as dysfunction and stem-like states leading to memory formation in T cells, are in intense focus of investigation. Here we show, by post hoc analysis of peripheral blood lymphocytes of hepatocellular carcinoma patients previously undergoing vaccination with tumour-associated antigen-derived peptides in our clinical trials (registration numbers UMIN000003511, UMIN000004540, UMIN000005677, UMIN000003514 and UMIN000005678), that induced peptide-specific T cell responses may persist beyond 10 years following vaccination. Tracking TCR clonotypes at the single cell level reveals in two patients that peptide-specific long-lasting CD8+ T cells acquire an effector memory phenotype that associates with cell cycle-related genes (CCNA2 and CDK1), and are characterized by high expression of IL7R, SELL, and NOSIP along with a later stage promotion of the AP-1 transcription factor network (5 years or more past vaccination). We conclude that effective anti-tumor immunity is governed by potentially proliferative memory T cells, specific to cancer antigens. The success of peptide vaccine treatment in cancer relies on the build-up of an efficient cytotoxic T cell response against the tumour antigen. Authors show here that tumour-specific memory CD8 T cells are able to persist and possibly even proliferate in the peripheral blood of long-surviving hepatocellular carcinoma patients.
- Subjects
PEPTIDES; T cells; CANCER patients; AP-1 transcription factor; IMMUNOLOGIC memory; CYTOTOXIC T cells; HEPATOCELLULAR carcinoma
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-30861-z