Antibody-Mediated phosphatidylserine blockade enhances the antitumor responses to CTLA-4 and PD-1 antibodies in melanoma

Bruce D. Freimark, Jian Gong, Dan Ye, Michael J. Gray, Van Nguyen, Shen Yin, Michaela M S Hatch, Christopher C W Hughes, Alan J. Schroit, Jeff T. Hutchins, Rolf A. Brekken, Xianming Huang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

In tumor-bearing animals, the membrane phospholipid phosphatidylserine (PS) suppresses immune responses, suggesting that PS signaling could counteract the antitumor effect of antibody-driven immune checkpoint blockade. Here, we show that treating melanoma-bearing mice with a PS-targeting antibody enhances the antitumor activity of downstream checkpoint inhibition. Combining PS-targeting antibodies with CTLA-4 or PD-1 blockade resulted in significantly greater inhibition of tumor growth than did single-agent therapy. Moreover, combination therapy enhanced CD4 and CD8 tumor-infiltrating lymphocyte numbers; elevated the fraction of cells expressing the proinflammatory cytokines IL2, IFNg, and TNFa; and increased the ratio of CD8 T cells to myeloid-derived suppressor cells and regulatory T cells in tumors. Similar changes in immune cell profiles were observed in splenocytes. Taken together, these data show that antibody-mediated PS blockade enhances the antitumor efficacy of immune checkpoint inhibition.

Original languageEnglish (US)
Pages (from-to)531-540
Number of pages10
JournalCancer Immunology Research
Volume4
Issue number6
DOIs
StatePublished - Jun 2016

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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