Dr. Wang on Challenges With Checkpoint Inhibitors in CRC

Timothy Cragin Wang, MD, Dorothy L. and Daniel H. Silberberg Professor of Medicine, chief, Division of Digestive and Liver Diseases, co-leader, Tumor Biology and Microenvironment Program, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, discusses the lack of response to checkpoint inhibitors in colorectal cancer (CRC).

Immunotherapy has revolutionized the treatment of patients with multiple tumor types, including melanoma, lung cancer, renal cell carcinoma, and some gastric cancers, says Wang. However, other diseases such as pancreatic cancer and most CRC cases are resistant to checkpoint inhibitors.

In CRC, patients without tumors that are microsatellite instability–high or mismatch repair deficient are unlikely to respond to checkpoint inhibitors, says Wang.

It is thought that these tumors are unresponsive because of immune resistance, says Wang. Moreover, resistance is thought to be promoted by the accumulation of immunosuppressive cells such as regulatory T cells, myeloid-derived suppressor cells (MDSCs), macrophages, and fibroblasts in the tumor microenvironment.

Preclinical models of MDSCs have shown promising efficacy in decreasing the number of immunosuppressive cells, which could lead to improved immune response in patients with microsatellite stable CRC, concludes Wang.