A comprehensive meta-analysis of tissue resident memory T cells and their roles in shaping immune microenvironment and patient prognosis in non-small cell lung cancer

Aidan Shen, Aliesha Garrett, Cheng Chi Chao, Dongliang Liu, Chao Cheng, Zhaohui Wang, Chen Qian, Yangzhi Zhu, Junhua Mai, Chongming Jiang

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification.

Original languageEnglish (US)
Article number1416751
Pages (from-to)1416751
JournalFrontiers in immunology
Volume15
DOIs
StatePublished - 2024

Keywords

  • machine learning
  • non-small-cell lung cancer
  • prognosis
  • tissue resident memory T cell
  • tumor immune microenvironment
  • Carcinoma, Non-Small-Cell Lung/immunology
  • Prognosis
  • Lung Neoplasms/immunology
  • Humans
  • Memory T Cells/immunology
  • Lymphocytes, Tumor-Infiltrating/immunology
  • Tumor Microenvironment/immunology
  • Immunologic Memory

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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