Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches

Clint T Allen, Paul E Clavijo, Carter Van Waes, Zhong Chen, Clint T Allen, Paul E Clavijo, Carter Van Waes, Zhong Chen

Abstract

Many carcinogen- and human papilloma virus (HPV)-associated head and neck cancers (HNSCC) display a hematopoietic cell infiltrate indicative of a T-cell inflamed phenotype and an underlying anti-tumor immune response. However, by definition, these tumors have escaped immune elimination and formed a clinically significant malignancy. A number of both genetic and environmental mechanisms may allow such immune escape, including selection of poorly antigenic cancer cell subsets, tumor produced proinflammatory and immunosuppressive cytokines, recruitment of immunosuppressive immune cell subsets into the tumor and expression of checkpoint pathway components that limit T-cell responses. Here, we explore concepts of antigenicity and immunogenicity in solid tumors, summarize the scientific and clinical data that supports the use of immunotherapeutic approaches in patients with head and neck cancer, and discuss immune-based treatment approaches currently in clinical trials.

Keywords: adaptive immunity; antigenicity; checkpoint inhibitors; immunogenicity; immunosuppression; immunotherapy; innate immunity; syngeneic mouse models; tumor antigen; vaccines.

Figures

Figure 1
Figure 1
Illustration of many of the mechanisms by which tumor cells, through deregulated oncogenic signaling pathways, induce the infiltration of different suppressive immune cells subsets into the tumor microenvironment. These include M2 (pro-tumor) macrophages, myeloid derived suppressor cells (MDSCs), regulatory T-lymphocytes and Th2 polarized CD4 T-lymphocytes. Many of these immune cells, in turn, directly suppress immune responses via cytokine production and release of immune-modulating enzymes. MDSCs within the tumor microenvironment can also contribute directly to tumor cell growth and survival via the secretion of cytokines and growth factors. While both tumor cells and immune cells can autonomously express checkpoint ligands such as PD-L1 downstream of oncogenic signaling pathways, this appears to be largely interferon responsive in HNSCC and serves to induce “adaptive resistance” in immunogenic tumors with high baseline interferon levels.

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