Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8+ T cells

• Published in: Nature communications Vol. 13; no. 1; p. 3123
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-06-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/31; 14/1; 14/19; 14/63; 38; 38/91; 631/250/2152/1566/1571; 631/250/580/1884/2323; 631/250/590/2030; 631/67/1059/2325; Activator protein 1; Anticancer properties; Antigens; Blood; Cancer; Cancer vaccines; CD8 antigen; Cell cycle; Clinical trials; Cytotoxicity; Effector cells; Hepatocellular carcinoma; Humanities and Social Sciences; Immune system; Immunological memory; Interleukin 7 receptors; Liver cancer; Lymphocytes; Lymphocytes T; Memory cells; multidisciplinary; Patients; Peptides; Peripheral blood; Phenotypes; Science; Science (multidisciplinary); T cell receptors; Transcription factors; Tumors; Vaccination; Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30861-z

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.