Overcoming melanoma resistance to immune checkpoint blockade therapy using nano-strategies

Monoclonal antibodies targeting CTLA-4, PD-1/PD-L1 axis, and LAG-3, have shown unprecedented clinical success in melanoma. However, such immune checkpoint blockade (ICB) therapies failed to initiate primary immune responses or with limited durability. Here, we reviewed the mechanisms eliciting intrinsic resistance and adaptive resistance in melanoma patients. Furthermore, we introduced emerging nano-strategies to overcome the ICB by either enhancing tumour cell phagocytosis through checkpoint-mediated internalization or devising nano-immunomodulators for ICB combination therapy. These strategies may lead to clinical translations in the future.