Tumours subvert the host immune system to enable their growth and thwart immunotherapy. A key mechanism employed by many advanced tumours involves the recruitment of immunosuppressive FOXP3+ regulatory T (Treg) cells that restrain anti-cancer responses. Specifically targeting tumour Treg cells is a major goal in immunotherapy. Using deep profiling of lung adenocarcinoma for immune and cell survival characteristics by CyTOF, we found “re-wiring” of cell death mechanisms specifically in Treg cells infiltrating tumours. This Treg cell survival switch was also observed in other tumour classes and mouse models of lung adenocarcinoma. In tumour-bearing mice, targeting the pro-survival characteristics of tumour-Treg cells with a BH3 mimetic drug in combination with anti-PD1 checkpoint blockade prolonged survival. These data uncover a conserved cell survival switch in tumour-infiltrating Treg cells that may be exploited to enhance response to immunotherapy.