For example, they can be performed with different (e.g., NK cells, as was done in (75), or ‘exhausted’ vs. polyfunctional T cells), or more complex co-culture systems (e.g., tumor : T cell : NK cell combinations), more environmental perturbations (e.g., nutrient starvation, hypoxia, highly acidic conditions), in in vivo mouse models (as in (5, 12, 13), in isogenic tumor cell lines with specific alterations [as was done in (5)] or even in combination with specific therapeutics (e.g. anti-CTLA-4 or anti-PD-1). The gene discussed is CTLA4; the disease is neoplasm.