Figure 6: Proposed mechanism underlying TCE treatment failure against tumors with low antigen density and synergy between TCE and IL2_REH combination therapy.

The untreated TME is characterized by low T cell infiltration and elevated CD8⁺ TIL exhaustion and Treg proportions, leading to unchecked tumor growth. TCE monotherapy drives recruitment of peripheral T cells into the TME which are dysfunctionally activated, leading to increased CD8⁺ TIL clonal diversity without significant changes in exhaustion and cytotoxicity signatures or Treg proportions, resulting in incomplete tumor control. TCE-IL2_REH combination therapy recruits peripheral T cells into the TME which are then successfully activated, leading to an increased population of clonally-diverse CD8⁺ TILs that are less exhausted and more capable of anti-tumor activity, resulting in immunogenic tumor control. Figure created using BioRender.