For example, nearly 40% of patients with metastatic melanoma, a disease with among the most immunotherapy successes, do not respond initially to combination cytotoxic T lymphocyte associated protein 4(CTLA-4) and PD-1 inhibition and of those that do respond, the duration of response is limited by as-yet undefined mechanisms of acquired resistance.22 23 Hence, there is a need for personalized models that faithfully reflect the TME of individual patients, and that can therefore be used to test primary and acquired resistance to therapies. Here, CTLA4 is linked to metastatic melanoma.