Glycolysis inhibition induces anti-tumor central memory CD8+T cell differentiation upon combination with microwave ablation therapy

  • 类型:
  • 作者:Tang Xinyu, Mao Xinrui, Ling Peiwen, Yu Muxin, Pan Hua, Wang Jiaming, Liu Mingduo, Pan Hong, Qiu Wen, Che Nan, Zhang Kai, Bao Feifan, Peng Hongwei, Ding Qiang, Wang Shui, Zhou Wenbin
  • 期刊:Nature Communications
  • 阅读原文

Minimally invasive thermal therapy is a successful alternative treatment to surgery in solid tumors with high complete ablation rates, however, tumor recurrence remains a concern. Central memory CD8 + T cells (T CM ) play important roles in protection from chronic infection and cancer. Here we find, by single-cell RNA analysis of human breast cancer samples, that although the memory phenotype of peripheral CD8 + T cells increases slightly after microwave ablation (MWA), the metabolism of peripheral CD8 + T cells remains unfavorable for memory phenotype. In mouse models, glycolysis inhibition by 2-deoxy-D-glucose (2DG) in combination with MWA results in long-term anti-tumor effect via enhancing differentiation of tumor-specific CD44 hi CD62L + CD8 + T CM cells. Enhancement of CD8 + T CM cell differentiation determined by Stat-1, is dependent on the tumor-draining lymph nodes (TDLN) but takes place in peripheral blood, with metabolic remodeling of CD8 + T cells lasting the entire course of the the combination therapy. Importantly, in-vitro glycolysis inhibition in peripheral CD8 + T cells of patients with breast or liver tumors having been treated with MWA thrice leads to their differentiation into CD8 + T CM cells. Our work thus offers a potential strategy to avoid tumor recurrence following MWA therapy and lays down the proof-of-principle for future clinical trials.

文章引用产品列表