Figure 3.

Tipping points induce dichotomous clinical outcomes in heterogeneous patient populations. (A) Treatments target processes or cell populations in the tumor microenvironment. (B, C) Two criteria need to be met to induce long-term survival: (B) ICI need to augment T cell killing sufficiently and (C) the treatment effect needs to be retained for a prolonged time. An inadequate treatment effect or limited treatment duration led at maximum to a temporary survival benefit. (D, E) In patient populations with variation in only (D) the tumor (ie, growth rate), or (E) the immune system (ie, T cell killing rate), the distance to a tipping point determines the clinical benefit. Without treatment, survival was limited (gray bars). In contrast, ICI induced long-term survival solely in patients close to a tipping point (green bars). See also online supplemental table 3. ICI, immune checkpoint inhibition; OS, overall survival.