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Homeostatic Dysregulation of Systemic CD8+ T Cell Compartment in Lung Cancer Patients

ABSTRACT: Cancer adapts to evolve various resistant mechanisms to counteract CD8+ T cell attacks. While this suppression for antigen-specific CD8+ T cells is common within the tumor microenvironment, little is known about how tumors affect overall CD8+ T cell compartment systemically. Here we show a new link in lung cancer patients between tumor-associated homeostatic dysregulation and uncontrolled differentiation of peripheral blood CD8+ T cells. These CD8+ T cells exhibited coordinated alterations indicative of reduced quiescence, increased spontaneous activation, and a progressive transition toward proliferation-incompetent late differentiated effector subsets. This phenomenon was not limited to tumor-reactive cells but was also broadly applicable to tumor non-specific cells, which correlated with poor clinical responses to immune checkpoint inhibitor therapy. Malignant diseases continue to confront newly primed CD8+ T cells, and here we uncover a new mechanism by which cancer impairs potentially tumor-reactive CD8+ T cells via dysregulating homeostasis of systemic CD8+ T cell populations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE247754 | GEO | 2025/06/16

REPOSITORIES: GEO

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