Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.

Fig. 1

The TME of HNSCC. The TME is composed of cancer cells and heterogenous nonmalignant cells integrated in a complex extracellular matrix (ECM). The main cellular components of the TME are T lymphocytes, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), natural killer (NK) cells, tumor-associated neutrophils (TANs), and cancer-associated fibroblasts (CAFs). Immune cells play a key role in tumor cell growth and dissemination

Fig. 2

Immunoregulators and immunotherapeutic strategies in HNSCC. The inflammatory state of the TME can modulate CD8⁺ T-lymphocyte response to cancer cells. Nonmalignant cells (CAFs, TANs, MDSCs, and Tregs) in the TME have been reported to inhibit CD8⁺ T-lymphocyte, while NK cells and Th lymphocytes both have CD8⁺ T-lymphocyte supportive functions. HNSCC is infiltrated with immune cells. Cetuximab, an EGFR inhibitor, was the first immune targeted therapy to be approved in HNSCC. PD-1 immune checkpoint inhibitor, nivolumab, and pembrolizumab have recently been granted approval for use in advanced or metastatic HNSCC. Immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4, TIM-3, and LAG-3) are important therapeutic targets for treatment and prevention of HNSCC