Advances in T-cell checkpoint immunotherapy for head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells “immune checkpoint” has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc). Current data suggest that PD-1 and CTLA-4 receptors can inhibit T-cell receptors and T-cell proliferation. Blockade of PD-1/PD-L1 and/or CTLA-4/CD28 pathways has shown promising tumor outcomes in clinical trials for advanced solid tumors like melanoma, renal cell cancer, and non-small cell lung cancer. The present review attempts to explore what is known about PD-1/PD-L1 and CTLA-4/CD28 pathways with a focus on HNSCC. We further discuss how these pathways can be manipulated with therapeutic intent.

The intracellular signalosome of PD-L1 in cancer cells

“… 8 Other PD-L1/PD-1 blocking antibodies, including nivolumab, atezolizumab, durvalumab and avelumab, have been approved for clinical use. 9 – 13 In 2017, pembrolizumab was the first FDA-approved immunotherapeutic agent for the treatment of solid tumors with unresectable mismatch-repair deficiency and microsatellite instability. 14 …”

Comprehensive gene cluster analysis of head and neck squamous cell carcinoma TCGA RNA‐seq data defines B cell immunity‐related genes as a robust survival predictor

“…Among these four gene clusters, we are particularly interested in the ones related to B cell receptor signaling pathway or B cell immunity, which have a favorable role in patient survival with HNSCC when expressed higher. Although the critical role of immune activity on cancer development, treatment, and prognosis have been more and more recognized in HNSCC, most of the findings were mainly related to T cell immunity, including its role in immunodeficiency or suppression in cancer development, antitumor therapy, and prognosis of HNSCC 34–38 . Roles of B cells in HNSCC are still not clearly understood.…”

Oral Microbiome and Response to Immunotherapy: Is It Time To Pay Attention?

“…PD-1 blockade has been shown to prevent the development of carcinogen-induced oral premalignant legions and prevent the malignant transformation [12,13]. While clinical studies of PD-1 blockade exclusively on oral squamous cell carcinoma (OSCC) are not available, study on head and neck squamous cell carcinoma (HNSCC) has shown that a subset of patients benefit from this treatment; leading to the approval of PD-1 blocking antibody for patients with platinum-refractory recurrent and/or metastatic HNSCC [14,15]. These findings, however, further highlight that a majority of the patients do not respond to this therapy.…”