The Use of Immune Regulation in Treating Head and Neck Squamous Cell Carcinoma (HNSCC)

Abstract

Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential for targeted and effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature and limited treatment options. Conventional therapies such as surgery, radiation, and chemotherapy often have limited success rates and can have significant side effects. Immunotherapy harnesses the power of the immune system to recognize and eliminate cancer cells, and thus represents a novel approach with the potential to improve patient outcomes. In the management of head and neck squamous cell carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive cell therapy (ACT) and immune checkpoint inhibitor therapy. In this review, we are focusing on the latter. Immune checkpoint inhibitors target proteins such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to enhance the immune response against cancer cells. The CTLA-4 inhibitors, such as ipilimumab and tremelimumab, have been approved for early-stage clinical trials and have shown promising outcomes in terms of tumor regression and durable responses in patients with advanced HNSCC. Thus, immune checkpoint inhibitor therapy holds promise in overcoming the limitations of conventional therapies. However, further research is needed to optimize treatment regimens, identify predictive biomarkers, and overcome potential resistance mechanisms. With ongoing advancements in immunotherapy, the future holds great potential for transforming the landscape of oral tumor treatment and providing new hope for patients.

Keywords: combination therapy; cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); head and neck squamous cell carcinoma (HNSCC); immune checkpoint inhibitors; immunotherapy; oral carcinoma; programmed cell death protein 1; programmed death ligand-1 (PD-1/PD-L1); tumor microenvironment.

Figure 1

Tumor stromal cells, including immune cells and non-immune cells, and their key markers. Key immune cells in the TME include Macrophages, Dendritic cells, MDSCs, Tcells, and Bcells. The non-immune cells include cancer-associated fibroblasts and endothelial cells. This figure was created with BioRender.com (accessed on 12 October 2023).

Figure 2

Action mechanisms of antibodies targeting PD-1, PD-L1, and CTLA-4. Immune checkpoint proteins PD-1 and PD-L1 are expressed in T cells, B cells, and antigen-presenting cells (APCs). High levels of PD-L1 expression hide cancer cells from T cells and enable them to grow unchecked. When PD-1 binds to PD-L1, T cells stop dividing and killing cancer cells. Through activation of PD-1/PD-L1 signaling, cancer cells evade immune responses. Inhibition of the PD-1/PD-L1 interaction by monoclonal antibodies overturns this process and augments activity. This allows T cells to become activated and kill cancer cells. This figure was created with BioRender.com (accessed on 10 October 2023).