FIGURE 2.

Hypothetical model of anti-PD-1 mAbs efficacy/inefficacy according to different subtypes of CRC tumors. MSI and ultramutated MSS tumors show high neoantigen load associated with a large infiltration of CD4 and CD8 T cells and an upregulation of immune inhibitory receptors, allowing the use of anti-PD-1 mAbs. In contrast, tumor escape mechanisms in MSS tumors rely on a downregulation of HLA class-I and class-II along with a high infiltration of MDSCs, and the level of T cells remains low. In addition, the weak expression of inhibitory receptors in these tumors does not allow the use of anti-PD-1 mAbs, apart from a restricted group of MSS tumors characterized by low intratumoral heterogeneity that shares several features with mutated tumors and that should be able to respond to anti-PD-1 mAbs.