Figure 4.

Solutions for hurdle 3: impaired TIL quality. (1) Targeting immunosuppressive cells such as CAFs, T_regs and tumor-associated macrophages (TAMs) depletes producers of immunosuppressive cytokines, thereby decreasing suppressive signals for T cells, improving their effector functions. (2) Direct blockade of immunosuppressive cytokines, instead of targeting their cellular producers, is able to achieve the same. (3) Addition of costimulation provides positive signals for T-cell effector functions and survival. (4) Providing sustaining cytokines can also improve T-cell functioning. (5) Blockade of immune checkpoints can prevent T-cell dysfunction and allow stronger anti-tumor responses.