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bioRxiv · 10.1101/2023.12.27.573474

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

Lee, S.-W.·Yun, J. S.·Kim, Y. J.·Kim, H.-O.·Cho, H.-J.·Park, C.-K.·Oh, I.-J.·Cho, J.-H.
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Abstract

Cancer adapts various resistance mechanisms to counteract CD8+ T cell attacks. While this suppression of antigen-specific CD8+ T cells is common within the tumor microenvironment, little is known about how tumors affect CD8+ T cells systemically. Here we show a new link between tumor-associated homeostatic dysregulation and uncontrolled differentiation of peripheral blood CD8+ T cells. These CD8+ T cells exhibited progressive alterations indicative of diminished quiescence, increased spontaneous activation, and more-differentiated proliferation-incompetent effector cells. This phenomenon was not limited to tumor-reactive cells but broadly applicable to non-specific cells, correlating with poor clinical responses to immune checkpoint inhibitor therapy. These findings provide a new mechanism by which cancer impairs CD8+ T cells by dysregulating the homeostasis of systemic CD8+ T cell populations. One-Sentence SummaryCancer-associated homeostatic dysregulation accelerates uncontrolled differentiation of systemic CD8+ T cells.

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Lee, S.-W., Yun, J. S., Kim, Y. J., Kim, H.-O., Cho, H.-J., Park, C.-K., Oh, I.-J., Cho, J.-H.. 2023-12-28. Homeostatic Dysregulation of Systemic CD8+ T Cell Compartment in Lung Cancer Patients. https://doi.org/10.1101/2023.12.27.573474

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