Issues

Cancer-derived exosomes have profound and broad effects in cell culture but understanding their role in vivo has been hindered in the absence of physiologically relevant models. In this issue, Gargiulo and colleagues provide comprehensive evidence in genetic mouse models that chronic lymphocytic leukemia (CLL)-secreted exosomes in vivo are taken up by T cells and contribute to CLL progression by suppressing antitumor immunity. As the cover illustrates, they find that in absence of exosomes (left side), CD8⁺ T cells (white) are metabolically fit, produce cytokines, and release cytotoxic granules directly to the CLL target cells to their rapid elimination. In presence of leukemia-associated exosomes (right side), CD8⁺ T-cell activity is inhibited by immune checkpoint receptor engagement and transfer of proteins and microRNAs. As a result, CD8⁺ T cells are metabolically altered and unable to produce polyfunctional cytokines or properly release cytotoxic granules. For details, see the article on p. 54 and accompanying commentary by Zhong and Guo on p. 5. Cover image by Ella Maru Studio.