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Human epidermal growth factor receptor 2 (HER2, encoded by ERBB2) is an oncogenic driver in multiple cancers. Beyond canonical signaling, HER2 remodels the tumor microenvironment by suppressing antigen presentation, enhancing checkpoint expression, and driving cytokine-mediated suppression. This remodeling creates an immune-resistant environment, posing a barrier to sustained tumor control. Improving efficacy of HER2-targeted strategies will revolve around these immunomodulatory features. Here, we discuss strategies to maximize the potential of HER2 targeting, with a focus on addressing HER2-driven immunomodulation.