Crucial Immunological Roles of the Invasion Front in Innate and Adaptive Immunity in Cervical Cancer
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Background: The immunostimulatory actions of innate and adaptive immune responses play a crucial role in the cancer-immunity cycle. Although cervical cancer (CC) exhibits a high recurrence rate, the relation with lymphocytes in the tumor tissue have not been analyzed.
Methods: We analyzed NKT, NK, and T cells, not only in peripheral blood (PB), but also tumor tissue through histological analysis from 23 patients with CC collected before treatment. A correlation of them between PB and the tumor tissue were assessed.
Results: We detected functional NKT and NKG2D NK cells and effector CD4 Tregs in PB. In the tumor, we detected the infiltration of LAG-3 TIM-3 CD4 and CD8 T cells rather than NK cells particularly in the invasion front (IF) by fluorescent multiplex immunohistochemistry. The heatmap and correlation analysis revealed that LAG-3 TIM-3 CD8 T cells are highly associated with CD69 CD103 exhausted CD8 T cells. We identified the statistical relationship between CD4Tregs in PB and the number of LAG-3 TIM-3 CD4 T cells in the IF, which may be related to recurrence in patients with CC.
Conclusions: LAG-3 TIM-3 T cells located in the IF may play a key role in regulation of the tumor immune microenvironment.