title: Tumor cell-intrinsic CD274/PD-L1: A novel metabolic balancing act with clinical potential.
abstract: Tumor expression of the immune co-signaling molecule CD274/PD-L1 was originally described as impeding antitumor immunity by direct engagement of its receptor, PDCD1/PD-1, on antitumor T cells. Melanoma-intrinsic PDCD1 was recently shown to promote tumor growth and MTOR signals in cooperation with tumor CD274, and sarcoma-intrinsic CD274 signaling promotes glucose metabolism to impede antitumor immunity. Our recent report shows that tumor cell-intrinsic CD274 promotes MTORC1 signaling in mouse melanoma and mouse and human ovarian cancer, inhibits autophagy and sensitizes some tumors to clinically available pharmacological autophagy inhibitors and confers resistance to MTOR inhibitors. Tumor CD274 could be a biomarker of autophagy or MTOR inhibitor response in selected tumors, and these inhibitors could improve anti-CD274 or anti-PDCD1 cancer immunotherapy. As we found that distinct tumor types exhibit this CD274-driven phenotype, it could be widely applicable.
authors.affiliation: a Graduate School of Biomedical Sciences , University of Texas Health Science Center , San Antonio , TX , USA.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Clark
authors.affiliation: b Department of Medicine , University of Texas Health Science Center , San Antonio , TX , USA.
authors.forename: Harshita B
authors.initials: HB
authors.lastname: Gupta
authors.affiliation: a Graduate School of Biomedical Sciences , University of Texas Health Science Center , San Antonio , TX , USA.|b Department of Medicine , University of Texas Health Science Center , San Antonio , TX , USA.|c Cancer Therapy & Research Center , University of Texas Health Science Center , San Antonio , TX , USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Curiel
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D060890:B7-H1 Antigen / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human
keywords: B7-H1; CD274; MTOR; PD-1; PD-L1; PDCD1; autophagy; cancer immunotherapy; melanoma; ovarian cancer; unfolded protein response