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Project

Deciphering and targeting novel immune-checkpoints engaged by dying cancer cells, to improve anti-cancer immunotherapy

Targeting immune-checkpoints (IC) that inhibit anti-cancer immunity, via IC-blockers (ICB), has revolutionized clinical oncology. Regrettably, only a subset of cancer patients respond to ICBs. Biomarker-guided, multimodal therapeutic regimen are predicted to vastly improve ICB's efficacy. Therein, one of the current strategies entails second-line application of ICBs targeting CTLA4 or PD1/PD-L1 following cytotoxic therapy. However, this strategy fails to account for the 'skewing' effects of cancer cell death on IC landscape. Such skewing may cause emergence of novel 'alternative' ICs - a notion supported by our patient tumour transcriptome analyses. A 'switch' to alternative ICs may render the tumour resistant to ICBs targeting CTLA4/PD1/PD-L1. Thus, identification of such novel ICs is vital for designing ‘smart’ multimodal therapies wherein ICBs are “matched” to the ICs preferentially engaged by dying cancer cells. Hence, this project aims to decipher the cross talk between therapy-induced cancer cell death and immune cell-linked ICs; and study its immunological implications, to create an effective combinatorial immunotherapy regimen.
Date:1 Oct 2019 →  30 Sep 2023
Keywords:Apoptosis, Biomarkers, Cancer cell death, Immune-checkpoints, Cancer Immunotherapy
Disciplines:Cancer therapy, Applied immunology, Cell death, Innate immunity