Emerging role of immune checkpoint inhibitors and predictive biomarkers in head and neck cancers

Elbehi, Attia M.; I, Anu R; Ekine-Afolabi, Bene; Cash, Elizabeth

doi:10.1016/j.oraloncology.2020.104977

Cited by 11 publications

(12 citation statements)

References 90 publications

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“…This combination showed promising survival outcomes despite a 40% decrease from the maximum standard dose of DTX [46]. Combining DTX with immune checkpoint inhibitors in HNSCC is also very promising [47].…”

Section: Discussionmentioning

confidence: 99%

Assessment of a Nano-Docetaxel Combined Treatment for Head and Neck Cancer

Lee

Mubasher

McKenzie

et al. 2021

Onco

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Objective: The combination of docetaxel (DTX) with Laser-Activated NanoTherapy (LANT), as a treatment for head and neck cancer (HNC), may enhance the therapeutic efficacy of lower doses of DTX, thereby minimizing the effective dosage, side effects and treatment times. Material and methods: Three HNSCC cell lines, Detroit 562, FaDu, and CAL 27, were treated with four combinations of DTX + LANT to evaluate DTX dose reduction and cell viability. Results: The 1 nM DTX + 5 nM LANT combination was the most effective treatment, increasing cell death over its corresponding DTX monotreatment with approximately 86.6%, 80.7%, and 92.1% cell death for Detroit 562, FaDu, and CAL 27, respectively. In Detroit 562, the 1 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 84.6%; in FaDu and CAL 27, the 0.5 nM DTX + 5 nM LANT combination treatment resulted in the highest percentage of DTX dose reduction at 78.2% and 82.4%, respectively. Conclusion: LANT may increase the therapeutic efficacy of DTX at significantly lower doses, which could improve patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Assessment of a Nano-Docetaxel Combined Treatment for Head and Neck Cancer

Lee

Mubasher

McKenzie

et al. 2021

Onco

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“…However, the role of ICI in OPSCC is still controversial, as only a small proportion of patients benefit from anti-PD-1 monotherapy or in combination with chemotherapy [ 18 ]. Therefore, several trials are currently ongoing to delineate new immunotherapy and combinatorial strategies effective for HNSCC patients [ 19 ]. Furthermore, the use of immunotherapy in a neoadjuvant setting is particularly attractive.…”

Section: Introductionmentioning

confidence: 99%

The immune microenvironment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma: a multiparametric quantitative and spatial analysis unveils a rationale to target treatment-naïve tumors with immune checkpoint inhibitors

Tosi

Parisatto

Menegaldo

et al. 2022

J Exp Clin Cancer Res

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Background Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and second-line settings. However, only 15–20% of patients benefit from this treatment, a feature increasingly ascribed to the peculiar characteristics of the tumor immune microenvironment (TIME). Methods Immune-related gene expression profiling (GEP) and multiplex immunofluorescence (mIF) including spatial proximity analysis, were used to characterize the TIME of 39 treatment-naïve oropharyngeal squamous cell carcinomas (OPSCC) and the corresponding lymph node metastases. GEP and mIF results were correlated with disease-free survival (DFS). HPV-positive tumors disclosed a stronger activation of several immune signalling pathways, as well as a higher expression of genes related to total tumor-infiltrating lymphocytes, CD8 T cells, cytotoxic cells and exhausted CD8 cells, than HPV-negative patients. Accordingly, mIF revealed that HPV-positive lesions were heavily infiltrated as compared to HPV-negative counterparts, with a higher density of T cells and checkpoint molecules. CD8+ T cells appeared in closer proximity to tumor cells, CD163+ macrophages and FoxP3+ cells in HPV-positive primary tumors, and related metastases. In HPV-positive lesions, PD-L1 expression was increased as compared to HPV-negative samples, and PD-L1+ tumor cells and macrophages were closer to PD-1+ cytotoxic T lymphocytes. Considering the whole cohort, a positive correlation was observed between DFS and higher levels of activating immune signatures and T cell responses, higher density of PD-1+ T cells and their closer proximity to tumor cells or PD-L1+ macrophages. HPV-positive patients with higher infiltration of T cells and macrophages had a longer DFS, while CD163+ macrophages had a negative role in prognosis of HPV-negative patients. Conclusions Our results suggest that checkpoint expression may reflect an ongoing antitumor immune response. Thus, these observations provide the rationale for the incorporation of ICI in the loco-regional therapy strategies for patients with heavily infiltrated treatment-naïve OPSCC, and for the combination of ICI with tumor-specific T cell response inducers or TAM modulators for the “cold” OPSCC counterparts.

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“…This can be explained by the already widely accepted concept of “field cancerization” described by Slaughter and co‐workers in 1953 8 . In recent decades, there has been a search for ideal molecular biomarkers associated with malignant transformation of OPMD and tumor progression of malignant tumors of the head and neck 9,10 . Epidermal growth factor receptor (EGFR) belongs to the Human Epidermal Growth Factor Receptor (HER) family of transmembrane receptors with tyrosine kinase activity, which are overexpressed in more than 90% of squamous cell carcinoma of the head and neck (HNSCC) 11,12 .…”

Section: Introductionmentioning

confidence: 99%

“…8 In recent decades, there has been a search for ideal molecular biomarkers associated with malignant transformation of OPMD and tumor progression of malignant tumors of the head and neck. 9,10 Epidermal growth factor receptor (EGFR) belongs to the Human Epidermal Growth Factor Receptor (HER) family of transmembrane receptors with tyrosine kinase activity, which are overexpressed in more than 90% of squamous cell carcinoma of the head and neck (HNSCC). 11,12 Numerous studies indicate increased expression and activity of membrane EGFR (mEFGR) in OPMD and OSCC, with the degree of expression dependent on the severity of the disease.…”

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confidence: 99%

Significance of nuclear EGFR and ABCG2 expression in malignant transformation of oral potentially malignant disorders

et al. 2022

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Background The purpose of this study was to investigate the expression of nuclear EGFR (nEGFR) and the stem cell marker ABCG2 in oral leukoplakia (OL) and oral erythroplakia (OE) and to assess their significance as prognostic biomarkers for malignant transformation. Methods In this study we included 50 patients with oral potentially malignant disorders (OPMD), 31 with OL and 19 with OE, in whom we examined the expression of nEGFR and ABCG2 by immunohistochemical methods. Results Twenty‐one (42%) of 50 patients with OL and OE developed oral squamous cell carcinoma (OSCC). The malignant transformation was increased 12,84‐fold (95% CI, 2.15–76.44, p = 0.005) in OPMD expressing both ABCG2 and nEGFR. Expression of nEGFR is a strong indicator of malignant transformation, unlike ABCG2 expression, respectively. Conclusions Determining the co‐expression of the biomarkers nEGFR and ABCG2 in OPMD may serve us to determine the risk of malignant transformation in OSCC.

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Emerging role of immune checkpoint inhibitors and predictive biomarkers in head and neck cancers

Cited by 11 publications

References 90 publications

Assessment of a Nano-Docetaxel Combined Treatment for Head and Neck Cancer

Assessment of a Nano-Docetaxel Combined Treatment for Head and Neck Cancer

The immune microenvironment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma: a multiparametric quantitative and spatial analysis unveils a rationale to target treatment-naïve tumors with immune checkpoint inhibitors

Significance of nuclear EGFR and ABCG2 expression in malignant transformation of oral potentially malignant disorders

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