Characteristics and impact of programmed death-ligand 1 expression, CD8+ tumor-infiltrating lymphocytes, and p16 status in head and neck squamous cell carcinoma

Ngamphaiboon, Nuttapong; Chureemas, Teeranuch; Siripoon, Teerada; Arsa, Lalida; Trachu, Narumol; Jiarpinitnun, Chuleeporn; Pattaranutaporn, Poompis; Sirachainan, Ekaphop; Larbcharoensub, Noppadol

doi:10.1007/s12032-018-1241-1

Cited by 38 publications

(45 citation statements)

References 32 publications

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“…The TME of OSCC supports adaptive immune responses that can be maintained through specific antigens [79]. Ngamphaiboon et al reported that 83.9% of OSCC samples in their cohort (n = 203) showed positive expression of PD-L1 [36], while Takahashi et al reported low expression in 40% and high expression in 60% of OSCC samples (n = 77) [42]. PD-1/PD-L1 expression in OSCC has also been associated with increased tumour-infiltrating lymphocytes (TILs) [60,68,70,81].…”

Section: Discussionmentioning

confidence: 85%

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Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

Kujan

Schaijik

Farah

2020

Cancers

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Cancers of the oral cavity cause significant cancer-related death worldwide. While survival rates have improved in recent years, new methods of treatment are being investigated to limit disease progression and to improve outcomes, particularly in oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). The emerging treatment modality of immunotherapy targets immune checkpoint molecules including PD-1 and its ligand PD-L1, CTLA-4, LAG-3, and TIM-3 to enhance the host immune response against tumours, and to limit the growth and progression of cancer cells. In this systematic review, we searched five databases for keywords pertaining to oral cancers and OPMDs, along with immune checkpoint inhibitors, in order to summarize the current status of their use and efficacy in these diseases. A total of 644 different articles were identified between 2004 and 2019, with 76 deemed suitable for inclusion in the study, providing a total of 8826 samples. Combined results show expression of PD-1 and PD-L1 in the majority of OPMD and OSCC samples, with expression correlating with increased progression and decreased survival rates. Immunotherapy agents pembrolizumab and nivolumab target PD-1 and have been shown to prolong survival rates and improve disease outcomes, especially in combination with chemotherapy or radiotherapy. Despite the equivocal nature of current evidence, there is support for the prognostic and predictive value of immune checkpoint molecules, especially PD-L1, and many studies provide support for the effective use of immune checkpoint inhibitors in the management of OSCC. Limited data is available for OPMD, therefore this should be the focus of future research.

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Section: Discussionmentioning

confidence: 85%

“…PD-L1 was the most studied biomarker, analyzed in 53 studies [10,11,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][34][35][36][37][39][40][41][42][43][44][45][46]48,50,54,[59][60][61]64,65,67,68,[70][71][72][74][75][76][77][78]80,81,86]...…”

Section: Resultsmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

Kujan

Schaijik

Farah

2020

Cancers

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“…PD-1 and PD-L1 expression currently remain the most significant tissue biomarkers. PD-L1 expression has been associated with postchemotherapy (docetaxel/platinum/5-fluorouracil regimen) status, 127 co-occurrence with p16 INK4 expression, 131 and poorer OS 124,126,128 (but improved RFS 125,129 and OS 125,130 ). Among these studies, associations between high PD-L1 expression and favorable OS were all demonstrated in post-surgery HNSCC patients.…”

Section: Predictive Tissue Markers For Egfrtargeted Therapymentioning

confidence: 99%

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

Hsieh

Wang

et al. 2019

Head & Neck

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Background Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies. Methods Recent, relevant peer‐reviewed evidence were critically reviewed and summarized. Results This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole‐exome or whole‐genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed. Conclusion Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies.

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“…As one of the major factors in immune checkpoint activity, the clinical relevance of PD-L1 in tumor cells and tumor microenvironments is currently the subject of intense investigation. It has been shown in some studies that high levels of PD-L1 in cancer cells correlate with SCCHN tumor size, presence of regional metastases (Moratin et al, 2019;Muller et al, 2017), and poor prognosis (de Vicente et al, 2019;Moratin et al, 2019;Muller et al, 2017;Ngamphaiboon et al, 2019;Yang, Zeng, et al, 2018), whereas other studies of SCCHN demonstrated no clinical significance (Cho, Yoon, Lee, Hong, & Hong, 2011;Mattox et al, 2017;Yoshida et al, 2018).…”

mentioning

confidence: 99%

PD‐L1 in squamous cell carcinoma of the oral tongue shows gender‐specific association with prognosis

Wilms

Boldrup

et al. 2020

Oral Diseases

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Objective To use alternative quantitation approaches to clarify the clinical implication of programmed cell death ligand 1 (PD‐L1) in squamous cell carcinoma of the oral tongue (SCCOT). Materials and Methods Ventana SP263 immunohistochemistry assay and a multiplicative QuickScore method were applied to quantify PD‐L1 in tumor and surrounding immune cells from 101 patients with SCCOT. Tumor‐infiltrating immune cells were estimated from bulk tissue transcriptional profiles of 25 patients. Circulating PD‐L1 levels were measured in serum from 30 patients using an electrochemiluminescence assay platform. Results We found higher tumor cell PD‐L1 levels in females than males (p = .019). For patients with low PD‐L1 in tumor cells, better survival was seen in males than females (overall survival p = .021, disease‐free survival p = .020). Tumor‐infiltrating natural killer T cells, immature dendritic cells, and M1 macrophages were positively associated with tumor cell PD‐L1 (p < .05). Conclusions Our data confirmed the significance of gender on tumor cell PD‐L1 expression and demonstrated combined effects of gender and PD‐L1 levels on clinical outcome in patients with SCCOT. The data also indicated the involvement of specific immune cell types in PD‐L1‐regulated immune evasion.

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Characteristics and impact of programmed death-ligand 1 expression, CD8+ tumor-infiltrating lymphocytes, and p16 status in head and neck squamous cell carcinoma

Cited by 38 publications

References 32 publications

Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

PD‐L1 in squamous cell carcinoma of the oral tongue shows gender‐specific association with prognosis

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