Oncogenic growth factor signaling mediating tumor escape from cellular immunity

- HER signaling mediates downregulation of HLA class I mediated antigen presentation.
- HER signaling regulates expression of PD-L1 in tumor cells.
- HER signaling mediates secretion of oncogenic cytokines by tumor cells.

Unrestrained growth factor signals can promote carcinogenesis, as well as other hallmarks of cancer such as immune evasion. Our understanding of the function and complex regulation of HER family of receptors has led to the development of targeted therapeutic agents that suppress tumor growth. However, these receptors also mediate escape from recognition by the host immune system. We discuss how HER family of oncogenic receptors downregulate tumor antigen presentation and upregulate suppressive membrane-bound or soluble secreted inhibitory molecules that ultimately lead to impaired cellular immunity mediated by cytotoxic T lymphocyte (CTL) recognition. Implementing this knowledge into new therapeutic strategies to enhance tumor immunogenicity may restore effector cell mediated immune clearance of tumors and clinical efficacy of tumor-targeted immunotherapy against HER receptor overexpression.