CXCR5CD8 T cells present elevated capacity in mediating cytotoxicity toward autologous tumor cells through interleukin 10 in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive subtype of non-Hodgkin's lymphomas, with limited treatment options in refractory and relapsed patients. Growing evidence supports the notion that CD8 T cell immunity could be utilized to eliminate B cell lymphomas. CXCR5CD8 T cell is a novel cell subtype and share CXCR5 expression with CD19 tumor cells. In this study, we investigated the frequency and function of existing CXCR5CD8 T cells in DLBCL patients. We found that DLBCL patients as a group demonstrated significantly higher level of CXCR5CD8 T cells than healthy individuals, with huge variability in each patient. Using anti-CD3/CD28-stimulated CD8 T cells as effector (E) cells and autologous CD19 tumor cells as target (T) cells, at high E:T ratio, no difference between the intensities of CXCR5CD8 T cell- and CXCR5CD8 T cell-mediated cytotoxicity were observed. However, at intermediate and low E:T ratios, the CXCR5CD8 T cells presented stronger cytotoxicity than CXCR5CD8 T cells. The expressions of granzyme A, granzyme B, and perforin were significantly higher in CXCR5CD8 T cells than in CXCR5CD8 T cells, with no significant difference in the level of degranulation. Tumor cells in DLBCL were known to secrete high level of interleukin 10 (IL-10). We therefore blocked the IL-10/IL-10R pathway, and found that the expressions of granzyme A, granzyme B, and perforin by CXCR5CD8 T cells were significantly elevated. Together, these results suggest that CXCR5CD8 T cells are potential candidates of CD8 T cell-based immunotherapies, could mediate elimination of autologous tumor cells in DLBCL patients, but are also susceptible to IL-10-mediated suppression.