Immunotherapy for Colorectal Cancer

A Review of Current and Novel Therapeutic Approaches

Aaron J. Franke; William Paul Skelton IV; Jason S. Starr; Hiral Parekh; James J. Lee; Michael J. Overman; Carmen Allegra; Thomas J. George


J Natl Cancer Inst. 2019;111(11):1131-1141. 

In This Article

Consensus Molecular Subtypes (CMS)

The understanding that genomic expression is closely related to cellular phenotype and biological tumor activity has led to extensive international efforts to define a transcriptomics-based classification system of CRC subtypes. Comprehensive analyses of genomic and epigenomic features recently enabled researchers to categorize a majority of CRC into one of four CMS subtypes based on their distinguishing features (Table 2): CMS1 (MSI-like), CMS2 (canonical), CMS3 (metabolic), and CMS4 (mesenchymal).[36]

The CMS1 group has increased expression of genes specific to cytotoxic lymphocytes and is associated with a good prognosis. Importantly, the influential immunosuppressive signature of CMS4 tumors, characterized by overexpression of cancer-associated fibroblasts and their coregulatory chemokines (VEGF, hepatocyte growth factor, and platelet-derived growth factor), result in a TME favoring tumor-associated inflammation, angiogenesis, and activation of TGF-β, conveying the poorer prognosis.[22,37]

Although these molecular subtypes have not been established as a therapeutic stratification tool at this time, comprehensive genomic databases have been constructed to facilitate further understanding of distinct biological CRC entities and their potential to respond to immunotherapy. There are ongoing efforts to characterize local and systemic antitumor immunity more closely, including immunophenotyping of the immune compartment and studying the interplay between immunotherapy and host gut microbiome.[37]