Autocrine and paracrine activities of DLBCL tumor cell–derived IL-10. (Left) In an autostimulatory loop, lymphoma cell–derived IL-10 activates STAT3 downstream of the IL-10 receptor, leading to upregulation of PD-L1 expression and downregulation of the calcium channel CACNA1C. (Right) Lymphoma cell–derived IL-10 exerts functions on several immune cell types localized in the LME, thus contributing to the composition and functionality of the LME. Red arrows depict inhibitory activities of IL-10; green arrows depict IL-10 activities that maintain the physiological cell phenotype in the LME. The biological consequences of autocrine and paracrine IL-10 activity are indicated in the yellow (tumor cell–intrinsic functions) and green (functions in the lymphoma microenvironment) boxes.