Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8+ T cells
Eishiro Mizukoshi, Hidetoshi Nakagawa, Toshikatsu Tamai, Masaaki Kitahara, Kazumi Fushimi, Kouki Nio, Takeshi Terashima, Noriho Iida, Kuniaki Arai, Tatsuya Yamashita, Taro Yamashita, Yoshio Sakai, Masao Honda, Shuichi Kaneko
Abstract
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.