Integrating these pieces of evidence, we propose a model of the systemic antitumor immunity that we observed in SB28 flank tumors treated with dual CTLA-4/PD-1 blockade: tumor antigen is processed and presented by cDC2s early in the life of the tumor, but it is not sufficient to activate CD4 T cells due to negative signals from PD-1 and CTLA-4. The gene discussed is CTLA4; the disease is neoplasm.