Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade

J Immunother Cancer. 2021 Apr;9(4):e002231. doi: 10.1136/jitc-2020-002231.

Abstract

Background: CD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy.

Methods: Here, we test this by combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled in lung and bladder cancer clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)).

Results: ITGAE was identified as the most significantly upregulated gene in inflamed tumors. Tumor CD103+ CD8+ TRM cells exhibited a complex phenotype defined by the expression of checkpoint regulators, cytotoxic proteins, and increased clonal expansion.

Conclusions: Our analyses indeed demonstrate that the presence of CD103+ CD8+ TRM cells, quantified by tracking intratumoral CD103 expression, can predict treatment outcome, suggesting that patients who respond to PD-1/PD-L1 blockade are those who exhibit an ongoing antitumor T-cell response.

Keywords: CD8-positive T-lymphocytes; biomarkers; gene expression profiling; immunotherapy; lymphocytes; tumor; tumor-infiltrating.

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antigens, CD / genetics*
  • B7-H1 Antigen / antagonists & inhibitors*
  • B7-H1 Antigen / immunology
  • Biomarkers, Tumor / genetics*
  • CD8-Positive T-Lymphocytes / immunology*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Databases, Genetic
  • Gene Expression Profiling
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Integrin alpha Chains / genetics*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Phenotype
  • Randomized Controlled Trials as Topic
  • Time Factors
  • Treatment Outcome
  • Tumor Microenvironment
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • Integrin alpha Chains
  • alpha E integrins
  • atezolizumab