The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches

Abstract

The immune system plays a fundamental role in preventing cancer development by recognising and eliminating tumour cells. The recent success in the field of immunotherapy has confirmed the potential to exploit the immune response as a cancer treatment. Head and neck squamous cell carcinoma (HNSCC) is a malignancy characterized by dismal prognosis and high mortality rate; low survival outcomes in combination with significant toxicity of current treatment strategies highlight the necessity for novel therapeutic modalities. HNSCC is a favourable disease for immunotherapy, as immune escape plays a key role in tumour initiation and progression. T-cell checkpoint inhibitors targeting programmed cell death protein-1 have emerged as novel immunotherapy agents showing remarkable efficacy in HNSCC. However, only a minority of patients derive benefit for single-agent immunotherapies. In this regard, combinatorial immunotherapy approaches represent an alternative strategy that might increase the number of patients who respond to immunotherapy. Focusing on HNSCC, this review will summarise novel combinations of immune checkpoint blockade with other immunotherapy treatment modalities.

Regulatory T cells expressing abundant CTLA‐4 on the cell surface with a proliferative gene profile are key features of human head and neck cancer

“…12 Immunotherapy for head and neck cancer using anticytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) Ab and anti-programmed death-1 (PD-1) Ab are ongoing. 13,14 Head and neck cancer contains large numbers of somatic mutations which can generate neoantigens to activate cytotoxic CD8 + T cells. [15][16][17] However, over half of patients do not receive the benefits of immunotherapy.…”

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

“…The use of checkpoint inhibitors in the management of patients with head and neck squamous cell carcinoma (HNSCC) has become increasingly common following successful early clinical trials. Additionally, it has been shown that blockade of programmed death‐1 (PD‐1) and/or programmed death ligand‐1 (PD‐L1) has positive therapeutic benefits in HNSCC patients . Moreover, PD‐1 and PD‐L1 have emerged as the key checkpoints that can be manipulated with inhibitory monoclonal antibodies.…”

“…Additionally, it has been shown that blockade of programmed death-1 (PD-1) and/or programmed death ligand-1 (PD-L1) has positive therapeutic benefits in HNSCC patients. [1][2][3][4][5][6][7] Moreover, PD-1 and PD-L1 have emerged as the key checkpoints that can be manipulated with inhibitory monoclonal antibodies. In this context, the expression profile of PD-L1 is typically evaluated to identify patients who can clinically benefit from such inhibitors.…”

Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers

“…In conclusion, our results demonstrated that ICM function in the immune‐checkpoint system but also have important roles for the elicitation of eTreg activation and functions, which might create a tumor suppressive immune microenvironment in HNSCC tissues. Many combination immunotherapies with immune‐checkpoint inhibitors are being investigated in clinical trials for HNSCC 59 . It is important to choose drug combinations that effectively inhibit eTreg functions and immune‐checkpoint systems to improve HNSCC immunotherapy.…”