Immune escape mechanisms in head and neck squamous cell carcinoma and implication for new immunotherapy approach

Purpose of review The aim of this review is to describe the major steps leading to the immunosuppressive tumor microenvironment and to summarize some of the new immunotherapies that interfere with these mechanisms. Recent findings Immunotherapy has improved the outcome of relapsed/metastatic head and neck squamous cell carcinoma (HNSCC). However, most patients still do not respond to treatment and median overall survival remains short with a modest rate of long-term survivors. There is a growing awareness that tumor immune-escape is a complex process that involves many redundant mechanisms other than immune check-points. They interfere with the innate immune response, activation of adaptive immune response, homing of effector T cells, their clonal expansion, viability, and efficiency. This abundance of immunosuppressive mechanisms explains the limited results achieved by immune checkpoint inhibitors. Combined treatments targeting different mechanisms of escape are in development to further improve the outcome of patients with HNSCC. Summary Many mechanisms favor tumor immune-escape. Each tumor exploits preferably some of them and the challenge is to understand which are the best targets in each tumor. This knowledge is an important tool to design future combination strategies based on strong biological rationales, which could offer better results than simple empirical combinations.
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: HEAD AND NECK: Edited by Joël Guigay Source Type: research

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Conclusions: HPD was frequent, but TGK of HPD patients treated with ICI did not differ from SF patients, suggesting that there is no relevant causal relationship between HPD and ICI. After initial PD with ICI, tumor growth deceleration was associated with better outcomes, indicating that TGKR might be useful to detect late responders, meriting prospective investigations. Materials and Methods: TGK ratio (TGKR) was defined as the ratio of TGK on ICI (TGKpost) to TGKpre. HPD was defined as TGKR ≥ 2. TGKR>1 indicated tumor growth acceleration, while 0
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Immunotherapy enhances a patient's own immune system to fight against malignancy and has become increasingly popular during the last decade. Tumor cells can escape destruction by the patient's immune system by overexpression of immunosuppressive molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death-1 (PD-1) receptor, and its ligand PD-L1. Immunotherapy agents target these inhibitors and basically reactivate the cytotoxic lymphocytes to destroy the tumor cells. Immunotherapy agents currently are FDA-approved for advanced malignancies including melanoma, Hodgkin lymphoma, head and neck...
Source: Contemporary Diagnostic Radiology - Category: Radiology Tags: ARTICLE Source Type: research
o Muto Ionna : Head and neck squamous cell carcinomas (HNSCCs) are a very heterogeneous group of malignancies arising from the upper aerodigestive tract. They show different clinical behaviors depending on their origin site and genetics. Several data support the existence of at least two genetically different types of HNSCC, one virus-related and the other alcohol and/or tobacco and oral trauma-related, which show both clinical and biological opposite features. In fact, human papillomavirus (HPV)-related HNSCCs, which are mainly located in the oropharynx, are characterized by better prognosis and response to ther...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
This article describes the role of immune therapy in HPV-associated HNSCC along with the evidence and perspective behind differing therapeutic considerations. PMID: 32293695 [PubMed - in process]
Source: Oncology (Williston Park, N.Y.) - Category: Cancer & Oncology Authors: Tags: Oncology (Williston Park) Source Type: research
AbstractBackgroundNivolumab improves overall survival (OS) in patients with platinum-refractory recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). In one study, however, Kaplan –Meier OS and progression-free survival (PFS) curves for the nivolumab and cytotoxic agent arms crossed at 3–6 months, suggesting that patients with initial resistance to immunotherapy might have better outcomes with cytotoxic treatment. Here, we explored the conditions and candidates which are predictive of nivolumab outcomes in R/M HNSCC.MethodsWe retrospectively reviewed the clinical records of 27 consecu...
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
Immunosuppressive myeloid cells activated in the tumor microenvironment (TME) are a critical limitation to the efficacy of immune checkpoint inhibitors (ICIs) in patients with head and neck squamous cell carcinoma (HNSCC). In preclinical models, antibody blockade of Semaphorin 4D (SEMA4D, CD100) reduced function and recruitment of immunosuppressive myeloid cells, while simultaneously restoring the ability of dendritic cells and cytotoxic T cells to infiltrate the TME. Importantly, this coordinated shift from immunosuppression to tumoricidal activity complemented effects of other immunotherapies in syngeneic tumor models, w...
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Immunology and Immunotherapy Source Type: research
Efficient use of nivolumab in recurrent/metastatic head and neck squamous cell carcinoma (r/mHNSCC) has been limited by the lack of a definitive predictive biomarker. We aimed to investigate the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and outcome of patients with r/mHNSCC treated with nivolumab.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Immunology and Immunotherapy Source Type: research
T cell-mediated anti-tumor immune responses are gated in part by the relative abundance of cytotoxic T cells (Teffs) and regulatory (Tregs) in the tumor microenvironment (TME) whereby Treg may impair the efficacy of Teffs. Tregs can affect Teff function by direct cell-to-cell contact or by secretion of soluble mediators, consistent with the hypothesis that proximity of Tregs to Teff within tumor tissues may have prognostic significance. Here we used a novel chromogenic multiplex assay to investigate the spatial relationship of these functionally diverse T cell subsets in HPV positive and HPV negative head and neck squamous...
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Immunology and Immunotherapy Source Type: research
We examined treatment patterns and estimated real-world time on treatment (rwToT) with IO and non-IO based therapies post-PbC in patients with R/M HNSCC.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Immunology and Immunotherapy Source Type: research
We report a series of patients with advanced head and neck cSCC treated with PD-1/PD-L1 blockade as first line systemic therapy.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: Tags: Management of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Source Type: research
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