26
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p class="first" id="P1">Although treatment with immune checkpoint inhibitors provides promising benefit for cancer patients, optimal use is encumbered by high resistance rates and requires a thorough understanding of resistance mechanisms. We observed that tumors treated with PD-1/PD-L1 blocking antibodies develop resistance through the up-regulation of CD38, which is induced by all-trans retinoic acid (ATRA) and IFN-β in the tumor microenvironment. <i>In vitro</i> and <i>in vivo</i> studies demonstrate that CD38 inhibits CD8 <sup>+</sup> T cell function via adenosine receptor signaling, and that CD38 or adenosine receptor blockade are effective strategies to overcome the resistance. Large datasets of human tumors reveal expression of CD38 in a subset of tumors with high levels of basal or treatment-induced T cell infiltration, where immune checkpoint therapies are thought to be most effective. These findings provide a novel mechanism of acquired resistance to immune checkpoint therapy and an opportunity to expand their efficacy in cancer treatment. </p>

          Related collections

          Author and article information

          Journal
          Cancer Discovery
          Cancer Discov
          American Association for Cancer Research (AACR)
          2159-8274
          2159-8290
          July 16 2018
          : CD-17-1033
          Article
          10.1158/2159-8290.CD-17-1033
          6205194
          30012853
          f9af6bfc-bf95-494e-88b2-4dc2b245fd39
          © 2018
          History

          Comments

          Comment on this article