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

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. CD3+CD8+CD4- cells from peripheral blood mononuclear cells (PBMCs) of 4 healthy individuals and 8 non-small cell lung cancer (NSCLC) patients were isolated using Fluorescence-activated cell sorting (FACS). These cells were stained with CITE-seq antibodies and used for a 12-plexed single cell RNA-sequencing (10X Genomics). Raw data are unavailable due to patient privacy concerns. Data are however available from the authors upon reasonable request and with permission of Chonnam National University Hwasun Hospital. ------------------------- Authors state "Raw data are unavailable due to patient privacy concerns."