Cancer cells evade the immune system through a variety of different mechanisms, including the inhibition of antitumor effector T cells via checkpoint ligand–receptor interaction. Moreover, studies have shown that blocking these checkpoint pathways can reinvigorate the antitumor immunity, thereby prompting the development of numerous checkpoint immunotherapies, several of which are now being approved to treat multiple types of cancer. However, only a fraction of patients achieves promising long-term outcomes in response to checkpoint inhibition, suggesting the existence of additional unknown tumor-induced immunosuppressive pathways. In this issue of the JCI, Klement and colleagues describe an additional pathway of T cell inhibition in cancer. Specifically, the authors demonstrate that downregulation of IRF8, a molecular determinant of apoptotic resistance, in tumor cells aborts repression of osteopontin, which in turn binds to its physiological receptor CD44 on activated T cells and suppresses their activation. These results suggest that osteopontin may act as another immune checkpoint and may serve as a target to expand the number of patients who respond to immune checkpoint inhibitor therapy.
Michael R. Shurin
Guidelines: The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. All accepted letters will be posted on our website within one week of acceptance. We reserve the right to edit any letter for length, content, and clarity. Authors of all accepted letters will be asked to preview any changes. Authors will be notified by e-mail if their letters were not accepted. As this is a final decision, no appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editors directly at editors@the-jci.org.