Abstract 289: The combination of CD40 agonism and PD-L1 blockade enhances anti-tumor immunity in a mouse syngeneic orthotopic pancreatic tumor model

Abstract

Abstract Infiltration of immunosuppressive myeloid cells into tumors correlates with poorer prognosis in many cancer types. The immunosuppressive effects of these cells help to create a microenvironment that may inhibit responses to T cell-directed immunotherapies. Anti-CD40 agonistic antibodies (αCD40) promote myeloid cell maturation, license cross-presentation of antigens to cytotoxic T cells, and enhance direct macrophage tumoricidal activity. We tested the hypothesis that αCD40 can improve responses to PD-L1 blockade via enhancing anti-tumor immunity in a syngeneic orthotopic mouse model of pancreatic cancer (Pan02). Whilst PD-L1 blockade alone had limited effect on tumor growth, we demonstrated that αCD40 drove antigen presenting cell maturation and systemic immune activation, inhibiting tumor growth and improving overall survival. αCD40 also induced upregulation of PD-L1 both systemically and within the tumor microenvironment. Furthermore, the combination of αCD40 and PD-L1 blockade led to enhanced tumor growth inhibition and improved anti-tumor immunity compared to either monotherapy alone. These data provide further support for the potential benefits of re-educating tumor myeloid cells. Citation Format: Nadia Luheshi, Jane Coates-Ulrichsen, James Harper, Gareth Davies, James Legg, Robert Wilkinson. The combination of CD40 agonism and PD-L1 blockade enhances anti-tumor immunity in a mouse syngeneic orthotopic pancreatic tumor model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 289. doi:10.1158/1538-7445.AM2015-289