Characterization of CD103+ CD8+ tissue-resident T cells in esophageal squamous cell carcinoma: may be tumor reactive and resurrected by anti-PD-1 blockade

Cancer Immunol Immunother. 2020 Aug;69(8):1493-1504. doi: 10.1007/s00262-020-02562-3. Epub 2020 Apr 13.

Abstract

Though therapy that promotes anti-tumor response about CD8+ tumor-infiltrating lymphocytes (TILs) has shown great potential, clinical responses to CD8+ TILs immunotherapy vary considerably, largely because of different subpopulation of CD8+ TILs exhibiting different biological characters. To define the relationship between subpopulation of CD8+ TILs and the outcome of antitumor reaction, the phenotype and function of CD103+ CD8+ TILs in esophageal squamous cell carcinoma (ESCC) were investigated. CD103+ CD8+ TILs were presented in ESCC, which displayed phenotype of tissue-resident memory T cells and exhibited high expression of immune checkpoints (PD-1, TIM-3). CD103+ CD8+ TILs were positively associated with the overall survivals of ESCC patients. This population of cells elicited potent proliferation and cytotoxic cytokine secretion potential. In addition, CD103+ CD8+ TILs were elicited potent anti-tumor immunity after anti-PD-1 blockade and were not affected by chemotherapy. This study emphasized the feature of CD103+ CD8+ TILs in immune response and identified potentially new targets in ESCC patients.

Keywords: CD103; Esophageal squamous cell carcinoma; Tissue-resident T cells; Tumor-infiltrating lymphocytes.

MeSH terms

  • 4-Nitroquinoline-1-oxide / toxicity
  • Adult
  • Aged
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Biomarkers, Tumor
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinogens / toxicity
  • Cohort Studies
  • Esophageal Neoplasms / chemically induced
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / chemically induced
  • Esophageal Squamous Cell Carcinoma / immunology
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Integrin alpha Chains / immunology
  • Integrin alpha Chains / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Survival Rate
  • Tumor Cells, Cultured
  • Tumor Microenvironment / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Biomarkers, Tumor
  • Carcinogens
  • Integrin alpha Chains
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • alpha E integrins
  • 4-Nitroquinoline-1-oxide