Oncogenic pathways as the basis of primary immune ignorance

The success of immune checkpoint inhibitor therapies (ICTs) to bring about durable clinical responses in a subset of patients with different cancer histologies is transforming cancer care. However, many patients do not benefit from single-agent ICT, including patients with melanoma and non-small cell lung cancer, which are often considered to be immunogenic tumor types. In addition, several other common solid tumors, such as breast, colon, and prostate cancers, have reported very low response rates. A growing body of evidence suggests that the majority of tumors may be categorized as being primary immune-ignorant tumors, hence precluding response to single-agent ICTs. The molecular mechanisms that govern the immune-ignorant phenotype are under intense investigation. This review focuses on how oncogenic pathways can promote the development of a primary immune-ignorant tumor.