Research progress in mechanisms and clinical applications of immune checkpoint inhibitors combined with anti-angiogenic drugs in the treatment of pMMR/MSS colorectal cancer

Colorectal cancer (CRC) is a highly prevalent malignant tumor worldwide. The emergence of immune checkpoint inhibitors (ICIs) has provided more therapeutic options. However, approximately 85% of proficient mismatch repair or microsatellite stable (pMMR/MSS) CRC cases have extremely low response rates to ICIs monotherapy. This resistance is attributed to the low tumor mutational burden, weak immunogenicity, and highly immunosuppressive tumor microenvironments, posing a major challenge to CRC immunotherapy.The combination of ICIs with anti-angiogenic drugs (AADs) (ICI-AAD therapy) has led to a novel therapeutic paradigm for CRC. This review summarizes the mechanisms behind and recent advances in the ICI-AAD therapy for pMMR/MSS CRC in general and key clinical studies such as AtezoTRIBE and CAPability-01 in particular. By elucidating the immunologically “cold tumor” pathophysiology of pMMR/MSS CRC and the synergistic interplay of ICI-AAD therapy, this study is expected to provide data for optimizing combinatorial immunotherapy for this subtype.