Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

Echarri, María J.; López-Martín, Ana; Hitt, Ricardo

doi:10.3390/cancers8030027

Cited by 45 publications

(34 citation statements)

References 101 publications

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“…S7), signifying that higher numbers of Tregs may "dampen" the function of cytotoxic T cells and reduce clonal expansion of neoantigen-specific T cells. This finding is in accordance with multiple studies supporting the importance of Tregs in SCCHN biology, with clinical trials actively investigating CTLA4 inhibition not only in recurrent/metastatic SCCHN, but also in the locoregionally advanced, curativeintent setting (23)(24)(25). No significant associations were found between GRZB, PRF1, as well as the remaining immune markers, with the TCRb DI.…”

Section: Association Of Intratumoral Immune Markers With Tcrb DIsupporting

confidence: 90%

Characterization of the T-Cell Receptor Repertoire and Immune Microenvironment in Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Saloura

Fatima

Zewde

et al. 2017

Clinical Cancer Research

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Purpose: Squamous cell carcinoma of the head and neck (SCCHN) is a lethal cancer with a suboptimal 5-year overall survival of approximately 50% with surgery and/or definitive chemoradiotherapy. Novel treatments are thus urgently awaited. Immunotherapy with checkpoint blockade has emerged as a promising option for patients with recurrent/metastatic SCCHN; however, it has not been investigated in the curative-intent setting yet. The purpose of this study was to investigate the T-cell receptor repertoire and the tumor microenvironment in tumor tissues of SCCHN patients with locoregionally advanced disease.Experimental Design: We performed T-cell receptor sequencing of tumor tissues from 44 patients with locoregionally advanced SCCHN prior to treatment with definitive chemoradiotherapy and correlated the T-cell clonality and the mRNA expression levels of immune-related genes with clinicopathologic parameters.Results: Clonal expansion of T cells was significantly higher in human papilloma virus (HPV)-negative compared with HPVpositive tumors, signifying more robust antigen presentation in HPV-negative tumors. The latter was supported by the higher percentage of HPV-negative tumors expressing HLA-A protein compared with HPV-positive tumors (P ¼ 0.049). Higher GRZB levels correlated significantly with longer recurrence-free survival (log-rank, P ¼ 0.003) independent of tumor size, nodal stage, and HPV status.Conclusions: Our findings support clonal expansion of T cells in SCCHN patients with locoregionally advanced disease and imply differences in the antigen presentation capacity between HPV-negative and HPV-positive tumors. Elevated GRZB mRNA levels may also serve as a favorable and independent predictor of outcome in SCCHN patients treated with chemoradiotherapy. These data provide rationale for the introduction of immunotherapeutic approaches in the curative-intent setting.

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Section: Association Of Intratumoral Immune Markers With Tcrb DIsupporting

confidence: 90%

Characterization of the T-Cell Receptor Repertoire and Immune Microenvironment in Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Saloura

Fatima

Zewde

et al. 2017

Clinical Cancer Research

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“…The need to minimize treatment‐related toxicity must be balanced with the need for treatment efficacy to maintain function and quality of life as well as oncologic control among long‐term survivors. Advances in radiotherapy technology are being sought in an effort to enhance the precision of radiation delivery to avoid treatment‐related toxicity and to allow radiation to be safely combined with molecularly targeted radiation sensitizers or modifiers, all with the ultimate goal of enhancing tumor cell killing and improving tumor control …”

Section: Introductionmentioning

confidence: 99%

Proton versus photon radiation–induced cell death in head and neck cancer cells

et al. 2018

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Background: Photon (X-ray) radiotherapy (XRT) kills cells via DNA damage, however, how proton radiotherapy (PRT) causes cell death in head and neck squamous cell carcinoma (HNSCC) is unclear. We investigated mechanisms of HNSCC cell death after XRT versus PRT. Methods: We assessed type of death in 2 human papillomavirus (HPV)-positive and two HPV-negative cell lines: necrosis and apoptosis (Annexin-V fluorescein isothiocyanate [FITC]); senescence (β-galactosidase); and mitotic catastrophe (γ-tubulin and diamidino-phenylindole [DAPI]). Results: The XRT-induced or PRT-induced cellular senescence and mitotic catastrophe in all cell lines studied suggested that PRT caused cell death to a greater extent than XRT. After PRT, mitotic catastrophe peaked in HPV-negative and HPV-positive cells at 48 and 72 hours, respectively. No obvious differences were noted in the extent of cell necrosis or apoptosis after XRT versus PRT. Conclusion: Under the conditions and in the cell lines reported here, mitotic catastrophe and senescence were the major types of cell death induced by XRT and PRT, and PRT may be more effective. K E Y W O R D Scell death mechanisms, head and neck cancer, photon radiotherapy, proton radiotherapy, radiation-induced cell death

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“…Recently, checkpoint inhibitors, such as mAbs against programmed death-1 receptor (PD-1) and its ligand (PD-L1), have shown promising therapeutic efficacy in both HPV-positive and -negative HNSCC (6)(7)(8). However, these agents confer a benefit in only a minority of patients (9,10), creating a demand to develop new strategies in cancer immunotherapy with defined immunologic mechanisms of action to treat metastatic and recurrent HNSCC tumors.…”

Section: Introductionmentioning

confidence: 99%

Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer

Sato-Kaneko¹,

Yao²,

Ahmadi³

et al. 2017

JCI Insight

228

180

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Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC)

Cited by 45 publications

References 101 publications

Characterization of the T-Cell Receptor Repertoire and Immune Microenvironment in Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Characterization of the T-Cell Receptor Repertoire and Immune Microenvironment in Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

Proton versus photon radiation–induced cell death in head and neck cancer cells

Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer

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