Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide with a poor prognosis and high mortality. More than two-thirds of HNSCC patients still have no effective control of clinical progression, and the five-year survival rate is < 50%. Moreover, patients with platinum-refractory HNSCC have a median survival of < 6 months. The significant toxicity and low survival rates of current treatment strategies highlight the necessity for new treatment modalities. Recently, a large number of studies have demonstrated that programmed cell death protein-1 (PD-1) and its ligand, programmed cell death protein ligand-1 (PD-L1) play an essential role in tumor initiation and progression. PD-1/PD-L1 blockade has shown a desired and long-lasting therapeutic effect in the treatment of HNSCC and other malignancies. However, only a small number of patients with HNSCC can benefit from PD-1/PD-L1 blockade monotherapy, while the majority of patients do not respond. To overcome the unsatisfactory therapeutic effect of PD-1/PD-L1 blockade monotherapy, combining other treatment options for HNSCC (including chemotherapy, radiotherapy, targeted therapy, and immunotherapy) in the treatment scheme has become a commonly used strategy. Herein, the potential mechanisms underlying the crosstalk between PD-1/PD-L1 blockade and its combinatorial therapies for HNSCC were reviewed, and it is hoped that the improved understanding of the crosstalk process would provide further ideas for the design of a combinatorial regimen with a higher efficiency and response rate for the treatment of HNSCC and other malignancies.
Highlights
Head and neck squamous cell carcinoma (HNSCC) includes squamous cell carcinomas that occurs in the nasopharynx, oropharynx, hypopharynx, and throat
Only a small number of patients with HNSCC can benefit from PD-1/PD-L1 blockade therapy
We summarized its combination with other current treatment options for HNSCC from their crosstalk in the tumor microenvironment (TME) (Figure 1) to the ongoing clinical trials (Table 1), in order to better understand the mechanism of interaction between PD-1/PD-L1 blockade and other cancer therapies, and to provide further ideas for the design of combinatorial regimen with a higher efficiency and response rate in HNSCC and other malignancies
Summary
Head and neck squamous cell carcinoma (HNSCC) includes squamous cell carcinomas that occurs in the nasopharynx, oropharynx, hypopharynx, and throat. Recent studies have revealed that HNSCC exhibits an enriched tumor immune landscape, and when HNSCC showed a clinical progression, the immune response elicited by the strong immunogenicity of HNSCC is usually suppressed Immunosuppressive cells, such as bone marrow-derived suppressor cells (MDSCs), M2type tumor-associated macrophages (TAMs), and regulatory T cells (Tregs) can build an immunosuppressive state in HNSCC tumor microenvironment (TME). We summarized its combination with other current treatment options for HNSCC (including chemotherapy, radiotherapy, targeted therapy, and immunotherapy) from their crosstalk in the TME (Figure 1) to the ongoing clinical trials (Table 1), in order to better understand the mechanism of interaction between PD-1/PD-L1 blockade and other cancer therapies, and to provide further ideas for the design of combinatorial regimen with a higher efficiency and response rate in HNSCC and other malignancies. From the immune side, multiple types of chemotherapeutic agents have been shown to promote lymphocyte infiltration
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