Abstract IA11: The immunotherapy faces of Interleukin-8 and CD137

Abstract

Abstract IL-8(CXCL-8) is a chemoattractant factor for myeloid leukocytes, that is produced in large quantities by many solid tumors. Interestingly its concentration in serum is a negative prognostic and is predictive of lack of response to the anti-PD-1 mAb nivolumab, as confirmed in large series of patients. As a neuthrophil chemoattractant, IL-8 produced in cancer tissue attracts myeloid-derived suppressor cells and correlates with poor T-cell infiltration and weak gamma-interferon gene signatures. An IL-8 blocking mAb is being developed in combination with PD-1 blockade for cancer therapy focusing on cases with high circulating levels of IL-8. CD137 (4-1BB) is a costimulatory receptor expressed on primed NK and T cells whose activation with agonists antibodies invigorates CTL responses to fight cancer. CD137 agonists are highly synergistic with adoptive T-cell therapy. Recent evidence shows that CD137-costimulation reprograms chromatin, modifying DNA methylation in the loci of immune –relevant genes and potently enhances the size and respiratory functions of mitochondria in human and mouse CD8 T cells. Metabolic and epigenetic effects of CD137 agonists are critical for the antitumor therapeutic effects. In combination immunotherapy, strategies of CD137 costimulation can be used to potentiate radiotherapy in a synergistic fashion. Multiple constructs based on CD137 agonists are being developed clinically by the pharmaceutical and biotech industries. Citation Format: Ignacio Melero. The immunotherapy faces of Interleukin-8 and CD137 [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr IA11.