Abstract 3694: The role of the p40 family in pancreatic cancer

Abstract

Abstract Pancreatic cancer is the fourth leading cause of cancer in the US, and mortality is rising rapidly with little improvement in survival rates. Treatment remains a major challenge of this disease and these poor outcomes have researchers targeting the tumor microenvironment for therapy. The diagnosis and therapeutic options remain an obstacle due to the immune system response and associated non- specific symptoms. Immunotherapy is an important treatment for pancreatic cancer, and its applications are currently being studied. Targeting T cells to recognize and kill tumor cells could be a potential strategy. Due to the behavior of pancreatic cancer and the tumor microenvironment, immunosuppressive cells such as myeloid - derived suppressor cells and regulatory T cells limit the efficacy of T cell infiltration. The cytokine interleukin-12 (IL-12) plays an essential role to regulate both innate (natural killer cells) and adaptive (cytokine T-lymphocytes) immunities in cancer therapies. IL-12 is composed of two subunits, p40 and p35. We found that various human pancreatic cancer cells produce greater levels of p40 monomer and p40 homodimer (p402), than IL-12, and IL-23. We further demonstrate that selective neutralization of p40 by p40 mAb (a3-3a), by p402 mAb (d7-12c) stimulated death in pancreatic cancer cells. Our studies aim to identify the roles of p40 and p402 in pancreatic cancer cells and underlie the importance of p40 monomer and p40 homodimer in helping cancer cells escape cell death. Citation Format: Monica Sheinin. The role of the p40 family in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3694.