Prognostic impact of p16 and PD-L1 expression in patients with oropharyngeal squamous cell carcinoma receiving a definitive treatment

Satô, Fumihiko; Ono, Takeharu; Kawahara, Akihiko; Kawaguchi, Toshihiko; Tanaka, H.; Shimamatsu, Kazuhide; Kakuma, Tatsuyuki; Akiba, Jun; Umeno, Hirohito; Yano, Hirohisa

doi:10.1136/jclinpath-2019-205818

Cited by 31 publications

(44 citation statements)

References 30 publications

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“…In accordance with previous reports, 22,31 we found a significant association between p16 expression and levels of PD-L1 expression on TCs and ICs, as well as between PD-L1 expression on ICs and CD8 + T-cell density. We showed differences between type I TIMs in p16 + tumors and type II TIMs in p16-tumors, which is consistent with the previous report.…”

Section: F I G U R Esupporting

confidence: 93%

“…TIL density; type III: TC-PD-L1+/ low CD8 + TIL density; and type IV: TC-PD-L1−/high CD8 + TIL density), as previously reported 22. Types I, II, III, and IV were found in 11 (17%), 15 (23%), 39 (60%), and 0 patients (0%), respectively.…”

supporting

confidence: 81%

“…We showed differences between type I TIMs in p16 + tumors and type II TIMs in p16-tumors, which is consistent with the previous report. 22 It is a well-known fact that patients with p16+ OPSCC have better outcomes. We observed a better OS also in the most unfavorable group of type III TIM in p16+ group in comparison with p16-group.…”

Section: F I G U R Ementioning

confidence: 99%

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The tumor immune microenvironment and its implications for clinical outcome in patients with oropharyngeal squamous cell carcinoma

Gurín

Slavík

Hermanová

et al. 2020

J Oral Pathology Medicine

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Background: We examined PD-L1 expression on tumor cells (TCs) and immune cells (ICs) and density of CD3 + and CD8 + tumor-infiltrating lymphocytes (TILs) in patients with oropharyngeal squamous cell carcinoma (OPSCC) and investigated their significance on clinicopathological characteristics and clinical outcomes. Methods: In a cohort of 65 patients treated by definitive intensity-modulated radiotherapy (IMRT) with curative intent, immunohistochemical analysis of PD-L1 expression on TCs and ICs, and TIL subtyping was performed on primary biopsy tumor tissues, followed by prognostic evaluation of these immune response-related parameters including classification into four tumor immune microenvironment (TIM) types. To evaluate HPV status, p16 immunohistochemistry was performed. Results: Densities of CD3 + and CD8 + TILs and PD-L1 expressions on TCs and ICs were significantly higher in p16+/HPV-mediated OPSCC. Patients with high densities of stromal CD8 + TILs displayed significantly better overall survival (OS) and progression-free survival (PFS). PD-L1 expression neither on tumor cells nor on immune cells affected survival outcomes. Distribution of TIM types based on the combination of PD-L1 expression on TCs and densities of CD8 + TILs is significantly different in p16+ compared with p16-OPSCC. In type III TIM (TC-PD-L1+/low CD8 + TIL density), significantly better OS was shown in p16+ group compared with p16-OPSCC. Conclusion: The prognostic and predictive role of tumor immune microenvironment was confirmed for patients with OPSCC. Combining HPV status with the evaluation of densities of CD8 + TILs and PD-L1 expression including TIM classification might be of high clinical interest and warrants further prospective evaluation.

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Section: F I G U R Esupporting

confidence: 93%

supporting

confidence: 81%

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The tumor immune microenvironment and its implications for clinical outcome in patients with oropharyngeal squamous cell carcinoma

Gurín

Slavík

Hermanová

et al. 2020

J Oral Pathology Medicine

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“…14,30) However, no worldwide consensus value for the PD-L1 expression is currently present, and there have been reports with diverse criteria of PD-L1 positivity ranged from 5% to even 20%. 25,31) In this study, we used IRS for determining the positivity of PD-L1 expression, because we thought that there should be consideration not only about stained range but also about intensity to rule out the false positive results on interpretation of IHC staining. This IRS method would be an arguable point in our study also with the scoring performed by a single pathologist, however, we sought to minimize above errors by repetitive meticulous examination on multiple slides from specimens with blinded clinical information to the head and neck specialized and experienced pathologist.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Combined Programmed Cell Death 1 Ligand and p16 Expression Predicting Responsiveness to Radiotherapy in Patients with Oropharyngeal Squamous Cell Carcinoma

Kwon¹,

Kim²,

Cho³

et al. 2019

Korean J Otorhinolaryngol-Head Neck Surg

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Background and Objectives This study examined the expressions of p16 and the programmed cell death 1 ligand (PD-L1) in patients with oropharyngeal cancer (OPC) treated with radiotherapy (RT) to identify the correlation between p16 and PD-L1 expression, and to examine the prognostic significance of these markers for OPC patients receiving RT. Subjects and Method Forty-eight OPC patients diagnosed and treated at a tertiary referral hospital were enrolled in this retrospective analysis. Patients were initially treated with RT or chemoradiotherapy (CRT) with curative intent and completed the planned schedule. Expression of p16 and PD-L1 by primary tumors was evaluated by immunohistochemistry, and results were interpreted separately and dichotomized according to outcome analyses. Results Of the 48 patients, 25 (52.1%) expressed p16 and 15 (31.3%) expressed PD-L1. Expression of these markers showed a mutual positive correlation (p=0.046). Positive PD-L1 expression was associated with poor complete remission (CR) rates after RT (p=0.040). Positive p16 expression was associated with better recurrence-free survival (RFS) (p=0.004) but not overall survival (OS) (p=0.192). PD-L1 expression showed no independent association with survival (p>0.05); however, PD-L1 expression tended toward poorer RFS, even in p16-positive individuals. Conclusion There was a positive correlation between the expression of p16 and PD-L1 in OPCs. PD-L1 expression was associated with poorer CR rates after RT or CRT. PD-L1 alone did not show an association with RFS or OS, but when combined with p16, it tended toward poorer RFS, even in p16-positive cases.

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“…In addition, nickel has also been shown to induce the silencing of p16 through CpG site hypermethylation and thereby escape cell senescence [44]. Specifically, using p53 heterozygous mice and Wistar rats, treatment with nickel sulfide promoted promoter hypermethylation of p16, a cyclin-dependent kinase inhibitor and tumor suppressor gene [49]. Previous studies have demonstrated that nickel induces site-specific DNA hypermethylation.…”

Section: Dna Hypermethylationmentioning

confidence: 99%

The Role of Non-Coding RNAs Involved in Nickel-Induced Lung Carcinogenic Mechanisms

Zhu

Chen

et al. 2019

Inorganics

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Nickel is a naturally occurring element found in the Earth’s crust and an International Agency for Research on Cancer (IARC)-classified human carcinogen. While low levels found in the natural environment pose a minor concern, the extensive use of nickel in industrial settings such as in the production of stainless steel and various alloys complicate human exposure and health effects. Notably, interactions with nickel macromolecules, primarily through inhalation, have been demonstrated to promote lung cancer. Mechanisms of nickel-carcinogenesis range from oxidative stress, DNA damage, and hypoxia-inducible pathways to epigenetic mechanisms. Recently, non-coding RNAs have drawn increased attention in cancer mechanistic studies. Specifically, nickel has been found to disrupt expression and functions of micro-RNAs and long-non-coding RNAs, resulting in subsequent changes in target gene expression levels, some of which include key cancer genes such as p53, MDM2, c-myc, and AP-1. Non-coding RNAs are also involved in well-studied mechanisms of nickel-induced lung carcinogenesis, such as the hypoxia-inducible factor (HIF) pathway, oxidative stress, DNA damage and repair, DNA hypermethylation, and alterations in tumor suppressors and oncogenes. This review provides a summary of the currently known epigenetic mechanisms involved in nickel-induced lung carcinogenesis, with a particular focus on non-coding RNAs.

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Prognostic impact of p16 and PD-L1 expression in patients with oropharyngeal squamous cell carcinoma receiving a definitive treatment

Cited by 31 publications

References 30 publications

The tumor immune microenvironment and its implications for clinical outcome in patients with oropharyngeal squamous cell carcinoma

The tumor immune microenvironment and its implications for clinical outcome in patients with oropharyngeal squamous cell carcinoma

Prognostic Value of Combined Programmed Cell Death 1 Ligand and p16 Expression Predicting Responsiveness to Radiotherapy in Patients with Oropharyngeal Squamous Cell Carcinoma

The Role of Non-Coding RNAs Involved in Nickel-Induced Lung Carcinogenic Mechanisms

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