Antitumour immunity regulated by aberrant ERBB family signalling

Aberrant signalling of ERBB family members plays an important role in tumorigenesis and in the escape from antitumour immunity in multiple malignancies. Molecular-targeted agents against these signalling pathways exhibit robust clinical efficacy, but patients inevitably experience acquired resistance to these molecular-targeted therapies. Although cancer immunotherapies, including immune checkpoint inhibitors (ICIs), have shown durable antitumour response in a subset of the treated patients in multiple cancer types, clinical efficacy is limited in cancers harbouring activating gene alterations of ERBB family members. In particular, ICI treatment of patients with non-small cell lung cancers with epidermal growth factor receptor (EGFR) alterations and breast cancers with HER2 alterations failed to show clinical benefits, suggesting that EGFR and HER2 signalling may have an essential role in inhibiting antitumour immune responses. Here, we discuss the mechanisms by which the signalling of ERBB family members affects not only autonomous cancer hallmarks, such as uncontrolled cell proliferation, but also antitumour immune responses in the tumour microenvironment and the potential application of immune-genome precision medicine into immunotherapy and molecular-targeted therapy focusing on the signalling of ERBB family members.