Abstract：
: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.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Qiu H,Hu X,Gao L,Chen L,Chen J,Yuan J,Huang C,Xu X,Yang Jdoi
10.1016/j.yexcr.2017.08.036subject
Has Abstractpub_date
2017-11-15 00:00:00pages
146-152issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(17)30457-3journal_volume
360pub_type
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