Stem-like PD-1 ⁺ TCF-1 ⁺ CD8 ⁺ T cells result from helpless priming and rely on CD4 ⁺ T-cell help to complete their cytotoxic effector differentiation

BACKGROUND: differentiation state that progresses into terminal exhaustion in cancer and chronic infection. These stem-like cells are important, since they are the responders to PD-1 targeted immunotherapy and a potential resource for antitumor immunity. METHODS: T-cell help in the immunogenic MC38 tumor model. RESULTS: T cells into helped cytotoxic effectors. CONCLUSIONS: T cells to drive their expansion and differentiation into cytotoxic effectors is therefore an important therapeutic challenge in cancer and other conditions that lead to T-cell exhaustion.