Interleukin 10 enhanced CD8+ T cell activity and reduced CD8⁺ T cell apoptosis in patients with diffuse large B cell...

The pleiotropic cytokine interleukin (IL)-10 is best characterized by its ability to downregulate inflammation and promote peripheral tolerance. On the other hand, IL-10 was also found to maintain the effector response of CD8⁺ T cells and promote the expansion of tumor-resident CD8⁺ T cells. In diffuse large B cell lymphoma (DLBCL), the role of IL-10 has been characterized in tumor cells but not in CD8⁺ T cells. We found that CD8⁺ T cells in DLBCL presented robust interferon (IFN)-γ expression early during TCR-activation but could not maintain this response later on, which was characterized by significantly lower CD8⁺ T cell degranulation and higher apoptosis. These observations were associated with higher PD-1 expression in DLBCL CD8⁺ T cells. Furthermore, the PD-1⁺ cells were strongly enriched in the IFN-γ⁺, but not the IFN-γ^-, fraction. Interestingly, exogenous IL-10 significantly improved the survival of DLBCL CD8⁺ T cells, and resulted in significantly higher IFN-γ, ganzyme A and granzyme B expression in the absence of CD19⁺ tumor cells, and significantly improved CD8⁺ T cell-mediated specific lysis of CD19⁺ tumor cells. IL-10 did not alter the expression of PD-1 in DLBCL CD8⁺ T cells, but curiously, IL-10-treated DLBCL CD8⁺ T cells were less susceptible to PD-L1-mediated apoptosis. We then demonstrated that IL-10 treatment significantly elevated the expression of pro-survival factor Bcl-2. Blocking IL-10 resulted in higher apoptosis, fewer IFN-γ⁺ CD8⁺ T cells, and lower Bcl-2 expression. IL-10 also significantly increased STAT3, but not STAT1, phosphorylation in CD8⁺ T cells. Together, these results suggested that IL-10 could enhance CD8⁺ T cell inflammation in DLBCL patients.