The two sides of HER2/neu: immune escape versus surveillance

• HER2 is often amplified and/or overexpressed in tumor cells of distinct origin.
• HER2 could induce humoral and adaptive immune responses.
• HER2 overexpression is associated with an immune escape phenotype.
• HER2 downregulates the MHC class I antigen processing machinery.
• Understanding the HER2-induced immune escape may improve HER2-directed therapies.

The oncogene HER2 is one of the prototypes for targeted immunotherapy of cancer using both monoclonal antibodies as well as T cell based immunotherapies. Effective humoral and cellular immune responses against HER2 can be induced, but these responses can be influenced by the effects of this oncogene on the target tumor cells. The processes involved in HER2-mediated adaptive and innate immunity and the molecular mechanisms underlying the escape of HER2-expressing tumor cells from immune surveillance, particularly from cytotoxic T cells, are discussed. Implementing this knowledge in clinical trials to revert immune evasion may help optimize immunotherapies directed against HER2-expressing tumors.