CD28 and colon carcinoma: Using immune-responsive MC38 colon carcinoma cells implanted in WT C57BL/6 mice and CD28AYAA mice, we found that disruption of CD28 PYAP ICD-mediated signaling severely limited the antitumor efficacy of anti-PD-1 antibody therapy (Fig. 2I), indicating that CD28 PYAP ICD-mediated downstream signaling and effector proteins such as ARS2 may be relevant to cancer immunotherapy.