A Th1-like CD4+ T-cell Cluster That Predicts Disease-free Survival in Early-stage Lung Cancer

Abstract

Perioperative immune checkpoint inhibitors have been shown to improve prognosis in early-stage lung cancer. However, no biomarkers are known to indicate the requirement for treatment. This study aimed to identify T-cell clusters responsible for antitumor immunity in patients with early-stage lung cancer. Preoperative blood samples from 50 consecutive patients with lung cancer who were diagnosed as operable and underwent complete resection were analyzed by mass cytometry. Patients were divided into two groups: no recurrence at a minimum observation period of 851 days (median observation period: 1,031.5 days) and recurrence by the last observation date. Mass cytometry and single-cell RNA sequencing analysis of lymph nodes (LN) and tumor-infiltrating T cells were also performed. CCR4^-CCR6⁺ Th7R showed discriminative ability between recurrence and non-recurrence patients with lung cancer. Patients with more than 3.04% Th7R showed significantly favorable disease-free survival. Th7R was a major component of CD4⁺ T cells in tumor microenvironments and LNs adjacent to lung cancer tissues and was the only cluster that decreased in peripheral blood after the removal of cancer tissues, suggesting that Th7R was primed and proliferated in tumor-draining LNs in the presence of cancer tissues. Th7R had the kinetics that antitumor T cells should have, as indicated by the cancer immunity cycle; thus, peripheral blood Th7R could represent the potency of tumor immunity by reflecting priming and proliferation in tumor-draining LNs and Th7R in the tumor microenvironment. Prediction using peripheral Th7R before surgery could allow the selection of patients who require perioperative drug therapy and optimize therapeutic interventions with clinical implications.

Significance: Peripheral Th7R, a Th1-like CD4⁺ T-cell cluster reflecting priming status in draining LNs and immune status in the tumor microenvironment, predicts disease-free survival after complete resection and has significant clinical relevance in selecting appropriate therapeutic interventions in patients with early-stage lung cancer.