2. Academic Validation
  3. Glycolysis inhibition induces anti-tumor central memory CD8+T cell differentiation upon combination with microwave ablation therapy

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

  • Nat Commun. 2024 May 31;15(1):4665. doi: 10.1038/s41467-024-49059-6.
Xinyu Tang # 1 2,  Xinrui Mao # 1 2,  Peiwen Ling # 1 2,  Muxin Yu # 1 2,  Hua Pan # 3,  Jiaming Wang 1 2,  Mingduo Liu 1 2,  Hong Pan 1 2,  Wen Qiu 4,  Nan Che 5,  Kai Zhang 2 6 7,  Feifan Bao 8,  Hongwei Peng 3,  Qiang Ding 1 2,  Shui Wang 9 10,  Wenbin Zhou 11 12
Affiliations

Affiliations

  • 1 Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China.
  • 2 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
  • 3 Department of General Surgery, Liyang Branch of Jiangsu Provincial People's Hospital, 70 Jianshe West Road, 213399, Liyang, China.
  • 4 Department of Immunology, Nanjing Medical University, Nanjing, 211166, China.
  • 5 Department of Rheumatology and Immunology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China.
  • 6 Pancreatic Center & Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
  • 7 Pancreas Institute of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
  • 8 The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
  • 9 Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China. shwang@njmu.edu.cn.
  • 10 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. shwang@njmu.edu.cn.
  • 11 Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China. zhouwenbin@njmu.edu.cn.
  • 12 Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. zhouwenbin@njmu.edu.cn.
  • # Contributed equally.
PMID: 38821965 DOI: 10.1038/s41467-024-49059-6
Abstract

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 (TCM) 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 CD44hiCD62L+CD8+ TCM cells. Enhancement of CD8+ TCM 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+ TCM 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.

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