Cytotoxic chemotherapy reduces T cell trafficking to the spleen by downregulating the expression of C-C motif chemokine ligand 21 and C-C motif chemokine ligand 19

摘要

T cells serve an important role in the destruction of tumor cells and clearing of foreign pathogens. Previous studies have suggested that the T cell immune response of tumor-bearing patients is significantly lower than that of healthy people, and the principal reason for this is lymphocytopenia, which is caused by repeated cycles of chemotherapy. In addition to lymphocytopenia, the present study revealed that cytotoxic chemotherapy also weakens the homing ability of T cells to the T-cell zone of the spleen, which decreases the possibility of encounters between antigen-specific T cells and dendritic cells presenting the appropriate antigen, thereby weakening the immune response of T cells. These changes are attributed to the lower expression of C-C motif chemokine ligand 21 (CCL21) and C-C motif chemokine ligand 19 (CCL19) in the spleen of secondary lymphoid organs (SLOs). Finally, the present study identified that chemotherapy affects the function and survival of fibroblastic reticular cells in SLOs, which are the main source of CCL21 and CCL19. These observations aid us in further understanding the mechanism that is responsible for the decreased T cell immune response following repeated cycles of chemotherapy.