PO-362 Rational designing combinatorial T-cell based immunotherapy by high-dimensional profiling

Abstract

IntroductionClinical benefit of immunotherapeutic approaches against cancer has been well established. However, the benefit of cancer patients was mostly noted as prolonged survival. The lack of full cancer eradication is linked to immunosuppressive and immune escape mechanisms. Combination immunotherapy to improve the efficacy and duration of the tumor-specific T cell response offers an attractive avenue to develop more effective cancer therapies.Material and methodsHere we aimed to decipher the mechanisms governing the PD-1/PD-L1 checkpoint blockade to rationally design combination immunotherapy to improve immunotherapeutic benefit. We established high-dimensional immune signatures of immunotherapy-specific of cell subsets utilising mass cytometry with 38 markers.Results and discussionsPD-L1 blockade induced the expansion of highly specific tumor-infiltrating CD4 and CD8 T cells, displaying both activating (ICOS) and inhibitory (PD-1, LAG-3) molecules. Expansion of these therapy-induced T cell subsets was observed three days after treatment and significantly expanded in time leading to tumour delay. By targeting the activating and inhibiting molecules on the T cells by agonistic and blocking antibodies, respectively, we were able to further restore the T cell dysfunction and thereby improving the therapeutic benefit of single immunotherapy.ConclusionThus, high-dimensional profiling is a powerful means for rational designing combinatorial T-cell based immunotherapies.