CD80 expression is upregulated by TP53 activation in human cancer epithelial cells

Oncoimmunology. 2021 Apr 5;10(1):1907912. doi: 10.1080/2162402X.2021.1907912.

Abstract

CD80 is recognized as one of the most potent costimulatory molecules by which immune cells limit cancer progression; however, the current understanding of the regulation of its expression on human tumor cells is limited. The TP53 tumor suppressor plays a critical role in cancer and its significant role in the control of immune responses is emerging. Here, we evaluated the role of TP53 as a regulator of CD80 expression in human cancer cells. A set of well-known TP53-reactivating compounds were used on TP53-wild-type, TP53-deficient, TP53-mutated and TP53-knockdown cancer cell lines to determine if TP53 can regulate CD80. CD80 expression was analyzed in samples from patients with TP53-active vs TP53-inactive Colon Adenocarcinomas (COAD) from TCGA panCancer Atlas. We report that the pharmacological activation of TP53 can stimulate the expression of CD80 in human tumor cells of epithelial origin. We also provide evidence that CD80 expression exhibits a strong correlation with TP53 activation in a subgroup of colon tumors with better overall survival. These results confirm the link between TP53 and immune surveillance in human cancer and provide the possibility that conventional TP53-activation approaches for tumoricidal effects may be repurposed for immunotherapy strategies.

Keywords: TP53; cancer; cd80; colon; immune surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-1 Antigen* / genetics
  • Cell Adhesion Molecules
  • Colonic Neoplasms* / genetics
  • Epithelial Cells
  • Humans
  • Immunotherapy
  • Tumor Suppressor Protein p53 / genetics

Substances

  • B7-1 Antigen
  • Cell Adhesion Molecules
  • TP53 protein, human
  • Tumor Suppressor Protein p53