About the Cover
The efficacy of immunotherapy can be limited by immunosuppressive mechanisms in the tumor microenvironment. One such mechanism that is exploited by tumor cells is the production of adenosine, which creates an immunosuppressive niche that inhibits the functions of multiple immune cell types. Willingham et al. developed an adenosine receptor antagonist, CPI-444. In multiple tumor models, comparison of mice with and without CPI-444 treatment demonstrates that the compound, administered as a single agent, neutralized adenosine-mediated suppression, resulting in reduced tumor growth, increased antitumor responses, and increased T-cell activation. When combined with immune checkpoint blockade, antitumor responses and tumor reduction were enhanced. Thus, CPI-444 is a potential therapeutic for solid tumors. Read more in this issue on page 1136. Original image is of CD73 expression in non–small cell lung cancer. Artwork by Lewis Long.