Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck

Park, Brian; Mattox, Austin K.; Clayburgh, Daniel; Patel, Mihir R.; Bell, R. Bryan; Yueh, Bevan; Leidner, Rom S.; Xiao, Hong; Couey, Marcus; Li, Shiting; Qin, Tingting; Sartor, Maureen A.; Cairns, Belinda; MacDonough, Tracy; Halliwill, Kyle; Deschler, Daniel G.; Lin, Derrick T.; Faquin, William C.; Sadow, Peter M.; Pai, Sara I.

doi:10.1016/j.oraloncology.2022.106183

Cited by 4 publications

(2 citation statements)

References 25 publications

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“…In addition, we observed an increased PD-L1 expression in recurrent tumors from irradiated patients, which has also been reported by others [30][31][32]. A recent study investigated the modulation of PD-L1 expression in irradiated head and neck cancer cell lines [33].…”

Section: Discussionsupporting

confidence: 89%

Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma

Steen,

Semmelmayer,

Flechtenmacher

et al. 2023

IJMS

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The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.

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Section: Discussionsupporting

confidence: 89%

Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma

Steen,

Semmelmayer,

Flechtenmacher

et al. 2023

IJMS

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“…Park et al 40 recently used paired local recurrences for chemo-radiation treated HNSCC to show discordance of PD-L1 varied as a function of site with oral cavity demonstrating higher discordance and variable discordance depending on the CPS threshold chosen for analysis. Even when the selection for low levels of PD-L1 is maximal, as in the context of clinical trials utilizing anti-PD1/PD-L1 antibody-based strategies, concordance of anti-tumor immunity, whether measured via PD-L1 IHC or gene expression (e.g.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Oropharyngeal Squamous Cell Carcinomas Maintain Anti-tumor Immunity and Multinucleation Levels Following Completion of Radiation

Castro,

Corredor,

Koyuncu

et al. 2023

Head and Neck Pathol

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Objective: Oropharyngeal squamous cell carcinoma (OPSCC) recurrence is almost universally fatal.Development of effective therapeutic options requires an improved understanding of recurrent OPSCC biology.Methods: We analyzed paired primary-recurrent OPSCC from Veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who received curative intent radiation-based treatment (with or without chemotherapy). Patient tumors were analyzed using standard immunohistochemistry and automated imaging of in ltrating lymphocytes and multinucleated tumor cells coupled to machine learning algorithms.Results:Primary and recurrent tumors demonstrated high concordance via p16 and p53 immunohistochemistry, with comparable levels of multinucleation. In contrast, recurrent tumors demonstrated signi cantly higher levels of CD8+ tumor in ltrating lymphocytes (p<0.05) and higher levels of PD-L1 expression (p<0.05).Conclusion: Exposure to chemo-radiation and recurrence following treatment does not appear deleterious to underlying biological characteristics and anti-tumor immunity of oropharyngeal cancer, suggesting that novel treatment regimens may be as effective in the salvage setting as in the de nitive intent setting.

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Assessing PD-L1 Expression in Head and Neck Squamous Cell Carcinoma: Trials and Tribulations

Bill,

Faquin,

Pai

2023

Head and Neck Pathol

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Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck

Cited by 4 publications

References 25 publications

Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma

Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma

Recurrent Oropharyngeal Squamous Cell Carcinomas Maintain Anti-tumor Immunity and Multinucleation Levels Following Completion of Radiation

Assessing PD-L1 Expression in Head and Neck Squamous Cell Carcinoma: Trials and Tribulations

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