Improving Anti-cancer Immunotherapy by Simultaneous Targeting Suppressive Tumor Microenvironment

Abstract

Recent advances in immunotherapy led to a breakthrough in cancer treatment, changing the algorithms of clinical cancer management.Notwithstanding this success, numerous immune escape mechanisms significantly hamper the long-term efficacy of immunotherapy.A growing body of evidence recognizes immunosuppressive tumor microenvironment (TME) as a major obstacle for effective anti-cancer immunotherapy.It is therefore postulated that multiple pathways in TME need to be targeted in support to the induction of tumor-specific effector immune cells.Our lab has developed a novel mRNA vaccination platform allowing for induction of strong anti-tumor immune responses in the context of cervical cancer.In our recent study, using a variety of in vivo and ex vivo techniques, we observed the existence of organ-specific microenvironments that differed in their immunosuppressive capacity.We demonstrated that the particularly hostile nature of genital tract TME could be alleviated using cisplatin.This data indicated that the induction of tumor-specific T cells accompanied by a simultaneous targeting of TME is a prerequisite for the improvement of adaptive anti-cancer immunotherapies, thereby emphasizing the need for a TME-tailored immunotherapy.