Figure 2.

Strategies to sensitize cold HNSCC to ICR blockade. A multipronged approach is needed to most effectively prime the tumor microenvironment for ICR blockade. The goal of immune priming is to release frequent oncogenic inhibitors of the innate and adaptive immune signaling, to expand the pool of tumor-specific CTLs, and to metabolically support the activation of antigen-presenting cells and effectors. Some immune-priming approaches have shown promises in HNSCC immunotherapy, including but not limited to cancer vaccines, radiotherapy, DNA damage–inducing chemotherapy, and metabolic reprograming agents. CTL, cytotoxic T lymphocyte; HNSCC, head and neck cancer squamous cell carcinoma; ICR, immune checkpoint receptor.