Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

Abstract

Immunotherapy has been recently approved for the treatment of relapsed and metastatic human papilloma virus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC). However, the response of patients is limited and the overall survival remains short with a low rate of long-term survivors. There exists growing evidence that complex and partially redundant immune escape mechanisms play an important role for the low efficacy of immunotherapies in this disease. These are caused by diverse complex processes characterized by (i) changes in the expression of immune modulatory molecules in tumor cells, (ii) alterations in the frequency, composition and clonal expansion of immune cell subpopulations in the tumor microenvironment and peripheral blood leading to reduced innate and adaptive immune responses, (iii) impaired homing of immune cells to the tumor site as well as (iv) the presence of immune suppressive soluble and physical factors in the tumor microenvironment. We here summarize the major immune escape strategies of HNSCC lesions, highlight pathways, and molecular targets that help to attenuate HNSCC-induced immune tolerance, affect the selection and success of immunotherapeutic approaches to overcome resistance to immunotherapy by targeting immune escape mechanisms and thus improve the HNSCC patients’ outcome.

Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies

“…After infection, EBV can regulate its own viral and non-viral protein expression within the host cell and, in case of malignancies, actively modulate the tumor phenotype and in turn the tumor/TME interaction [131]. Although highly variable, the density of lymphocytes and plasma cells within the tumor stroma and of EBV-associated malignancies is elevated when compared to EBV-negative neoplasia as seen in other virus-associated tumors [132,133]. Furthermore, multiple viral infections within the same tumors could influence the TME [105].…”

Associations between dynamic-contrast enhanced MRI and tumor infiltrating lymphocytes and tumor-stroma ratio in head and neck squamous cell cancer

“…Interestingly, even neoangiogenesis related immunohistochemical parameters, such as vascular endothelial growth factor and hypoxia inducible factor 1-alpha showed associations with histogram parameters in HNSCC [ 11 , 13 ]. In a recent study, investigating several immunohistochemical features, only a correlation between K trans and p53 was identified [ 7 ].…”

“…There is growing interest on the field regarding tumor-infiltrating lymphocytes (TIL) around oncology [ 12 , 13 ]. The complex tumor microenvironment is of special interest as the communication between tumor and immune cells modulates tumor progress and treatment response [ 14 ].…”

Treg: A Promising Immunotherapeutic Target in Oral Diseases

“…Immune escape is a characteristic of head and neck squamous cell carcinoma (HNSCC) ( 84 ). Treg cells might contribute to the occurrence and progression of HNSCC by suppressing antitumor immunity ( 85 ).…”