About the Cover
Complement is known to play a role in antitumor immunity. However, specific complement molecules can be enriched in the tumor microenvironment where they can regulate the function of tumor and immune cells to promote tumor progression, and thus, interfere with immune-checkpoint blockade efficacy. Zha et al. show that expression and activation of complement C3 in murine tumor cells created an immunosuppressive milieu by facilitating the accumulation and suppressive function of tumor-associated macrophages, mediated by signaling through the C3a receptor. Deletion of C3 in the tumor cells enhanced the efficacy of checkpoint blockade, illustrating the potential of targeting tumor cell-derived complement to boost responses to immune-checkpoint blockade. Read more in this issue on page 193. Original image from Fig. 1D. Artwork by Lewis Long.