Tumor-Specific T Cells Exacerbate Mortality And Immune Dysregulation During Sepsis
JOURNAL OF IMMUNOLOGY(2021)
摘要
Sepsis induces significant immune dysregulation characterized by lymphocyte apoptosis and alterations in the cytokine milieu. Because cancer patients exhibit a 10-fold greater risk of developing sepsis compared with the general population, we aimed to understand how pre-existing malignancy alters sepsis-induced immune dysregulation. To address this question, we assessed the impact of tumor-specific CD8(+) T cells on the immune response in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. Tumor-bearing animals containing Thy1.1(+) tumor-specific CD8(+) T cells were subjected to CLP, and groups of animals received anti-Thy1.1 mAb to deplete tumor-specific CD8(+) T cells or isotype control. Results indicated that depleting tumor-specific T cells significantly improved mortality from sepsis. The presence of tumor-specific CD8(+) T cells resulted in increased expression of the 2B4 coinhibitory receptor and increased apoptosis of endogenous CD8(+) T cells. Moreover, tumor-specific T cells were not reduced in number in the tumors during sepsis but did exhibit impaired IFN-gamma production in the tumor, tumor draining lymph node, and spleen 24 h after CLP. Our research provides novel insight into the mechanisms by which pre-existing malignancy contributes to increased mortality during sepsis.
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