Current status and perspective of tumor immunotherapy for head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) have a high incidence and mortality rate, and investigating the pathogenesis and potential therapeutic strategies of HNSCC is required for further progress. Immunotherapy is a considerable therapeutic strategy for HNSCC due to its potential to produce a broad and long-lasting antitumor response. However, immune escape, which involves mechanisms including dyregulation of cytokines, perturbation of immune checkpoints, and recruitment of inhibitory cell populations, limit the efficacy of immunotherapy. Currently, multiple immunotherapy strategies for HNSCC have been exploited, including immune checkpoint inhibitors, costimulatory agonists, antigenic vaccines, oncolytic virus therapy, adoptive T cell transfer (ACT), and epidermal growth factor receptor (EGFR)-targeted therapy. Each of these strategies has unique advantages, and the appropriate application of these immunotherapies in HNSCC treatment has significant value for patients. Therefore, this review comprehensively summarizes the mechanisms of immune escape and the characteristics of different immunotherapy strategies in HNSCC to provide a foundation and consideration for the clinical treatment of HNSCC.

The Concordant Disruption of B7/CD28 Immune Regulators Predicts the Prognosis of Oral Carcinomas

“…As CTLA4 and PD-1 are inhibitory immune regulators, the survival implications seem to conflict with their presumed functions. These preliminary findings in the tumor samples contradict the use of CTLA4 and PD-1 blockers as therapeutics [ 24 ]. The typing of immune infiltration cells or annotation of immune regulators in the HNSCC TME is necessary prior to therapy.…”

“…Correlations between the upregulation of CD80, CD86, and CD28 have been found in OSCC [ 3 ], and the lack of change in CD28 and PD-1 transcripts in our tumor samples, which might have been associated with the complexity in CTLA4 abundancy [ 9 , 10 ], requires further stratification. Since a correlation in the expression of multiple immune regulators has also been found in OSCC, targeting only one molecule may have limited therapeutic efficacy [ 24 ].…”

“…Antitumor immune responses are an emerging strategy in HNSCC therapy [ 2 ]. Reports have shown that approximately 15% of patients with metastatic HNSCC exhibit responses to anti-PD-1 therapy [ 3 , 24 ]. Moreover, neoadjuvant anti-PD-1/PD-L1 immunotherapy may have advantages in operable HNSCC according to histopathological evaluation [ 25 ].…”

“…Due to the pluripotent roles of CD276 in HNSCC pathogenesis, and since CD276 is a predictor for the responses to immunotherapy in HNSCC [ 20 ], the combined efficacies of anti-PD-1 and anti-CD276 targeting have been tested in advanced HNSCC [ 28 ]. Many clinical trials attempting to abrogate or enrich the activity of B7/CD28 members are ongoing for HNSCC immunotherapy [ 23 , 24 ]. Although the functional activity and expression pattern of individual B7/CD28 members in HNSCC have been defined, since the functions of these molecules could be compensative, a comprehensive judgment of the prognostic value of B7/CD28 immune checkpoints in OSCC was needed.…”

Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma—A Review

“…From the immunopathology point of view, the majority of HNSCCs tend to exhibit an immune-depleted phenotype upon histology [ 127 , 128 ]. Some of the immune escape mechanisms of HNSCC include the recruitment of inhibitory cell populations such as Treg, MDSC, TAM, and CAF; perturbation by ICs such as PD-1 and CTLA-4, leading to T cell exhaustion; dysregulation of pro-proliferative cytokines such as TGF-beta, IL-6, and IL-10, as well as signaling pathways such as STAT-3; and increased physical barriers that hinder the infiltration of effector T cells and other immune cells [ 129 , 130 , 131 ]. Interestingly, several of these immunological aberrations can be targeted and reprogrammed by therapeutic vaccines, thus enhancing anti-tumor immunity.…”