CELL INTELLIGENCE · 肿瘤细胞治疗研究

Suppression of tumor-reactive CD8 + T cells is common within the tumor microenvironment. However, little is known about how tumors systemically affect the overall CD8 + T cell compartment. Here we demonstrate that peripheral blood CD8 + T cells from patients with lung cancer showed altered compositions particularly within CD45RA - CCR7 - effector memory subpopulation. Specifically, patients with lung cancer exhibited increased frequency of more differentiated effector memory cells, which are less susceptible to T cell-receptor-induced proliferation. Further analysis using single-cell RNA sequencing revealed that these alterations were correlated with reduced quiescence and increased spontaneous activation at a systemic level, indicative of homeostatic dysregulation of the entire CD8 + T cell population. This phenomenon was found to be correlated with a poor clinical response to immune checkpoint inhibitor therapy across four independent cohorts, consisting of a total of 224 patients with lung cancer. These findings suggest that lung cancers continue to counteract potentially tumor-reactive CD8 + T cells by inducing homeostatic dysregulation of the entire CD8 + T cell compartment systematically.