By contrast, CTLA-4 editing illustrates the context dependence of multiplex strategies: loss of CTLA-4 unleashes CD28 costimulation and stabilizes CAR surface expression under high antigen load, improving tumor control when targeted alone, yet this benefit is not recapitulated when CTLA-4 and PD-1 are co-edited—pointing to non-additive or even countervailing circuit interactions 101. Here, CTLA4 is linked to neoplasm.