IL-1/IL-1R Signaling in Head and Neck Cancer

Niklander, Sven; Murdoch, Craig; Hunter, Keith D.

doi:10.3389/froh.2021.722676

Cited by 16 publications

(10 citation statements)

References 170 publications

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“…Therefore, targeting senescent cells to reduce inflammation seems a promising approach to find new treatment alternatives to improve treatment success. The increased expression of NF- κ B signaling pathway ( 121 , 122 ) and NF- κ B-mediated cytokines ( 120 ), such as IL-1 in OPMD and OSCC, are reported to have impact in clinical outcomes ( 120 , 123 ). IL-1 is considered a master regulator of the SASP and for the spread of paracrine senescence ( 40 ), and there is evidence from in vivo animal studies that IL-1 induces malignant transformation of oral precursor lesions and OSCC aggressiveness ( 124 ).…”

Section: Discussionmentioning

confidence: 99%

Aging and oral squamous cell carcinoma development: the role of cellular senescence

Niklander,

Aránguiz,

Faunes

et al. 2023

Front. Oral. Health

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The gradual accumulation and inadequate renewal of senescent cells over time drive organismal aging. Senescent cells undergo altered gene expression and release inflammatory mediators collectively termed the senescence-associated secretory phenotype (SASP), which significantly contributes to a spectrum of age-related disorders, including cancer. In the context of carcinogenesis, the SASP produced by senescent cells has been implicated in the promotion of epithelial cancers, including oral squamous cell carcinoma (OSCC), the most common form of oral cancer. Senescent cells within the tumor microenvironment release factors that amplify the growth and invasiveness of neighboring cancer cells. Senotherapeutics, including senolytics and senomorphics, emerge as promising modalities to target senescent cells and their associated inflammatory factors, thereby opening novel avenues for augmenting the efficacy of cancer treatments. Here, we review the general aspects of cellular senescence, focusing on the relation between senescence-related inflammation with cancer development. We also analyze the available evidence linking cellular senescence with OSCC, highlighting possible clinical applications.

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Section: Discussionmentioning

confidence: 99%

Aging and oral squamous cell carcinoma development: the role of cellular senescence

Niklander,

Aránguiz,

Faunes

et al. 2023

Front. Oral. Health

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“…In HNSCC mouse xenografts, IL1-suppression by the drug anakinra was able to sensitize tumor cells toward EGFR inhibitor treatment (62). In such a context, IL1A could also reach clinical relevance, but clinical trials using anakinra in treatment of HNSCC patients are still outstanding (63).…”

Section: Discussionmentioning

confidence: 99%

IL1 Pathway in HPV-Negative HNSCC Cells Is an Indicator of Radioresistance After Photon and Carbon Ion Irradiation Without Functional Involvement

et al. 2022

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BackgroundTreatment of locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC) with photon radiation is the standard of care but shows only moderate success. Alterations in response toward DNA DSB repair, apoptosis, and senescence are underlying determinants of radioresistance in the tumor cells. Recently, senescence and the associated secretory phenotype (SASP) came into the focus of research and raised the need to identify the tumor-promoting molecular mechanisms of the SASP. The aim of this project was to unravel more of this process and to understand the impact of the IL1 pathway, which plays a major role in SASP. The studies were performed for photon and 12C-ion irradiation, which strongly vary in their effect on radioresistance.Materials and MethodsA panel of five HPV-negative HNSCC cell lines was treated with photon and 12C-ion irradiation and examined for clonogenic survival, DNA DSB repair, and senescence. SASP and IL1 gene expressions were determined by RNA sequencing and activation of the IL1 pathway by ELISA. A functional impact of IL1A and IL1B was examined by specific siRNA knockdown.ResultsCell killing and residual DSBs were higher after 12C-ion than after photon irradiation. 12C-ion induced more senescence with a significant correlation with cell survival. The impact on radioresistance appears to be less than after photon irradiation. The expression of SASP-related genes and the IL1 pathway are strongly induced by both types of irradiation and correlate with radioresistance and senescence, especially IL1A and IL1B which exhibit excellent associations. Surprisingly, knockdown of IL1A and IL1B revealed that the IL1 pathway is functionally not involved in radioresistance, DSB repair, or induction of senescence.ConclusionsIL1A and IL1B are excellent indicators of cellular radioresistance and senescence in HNSCC cells without functional involvement in these processes. Clearly more research is needed to understand the molecular mechanisms of senescence and SASP and its impact on radioresistance.

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“…Saliva is probably the most attractive secretion for the finding of biomarkers for OSCC and OPMDs, as its collection is easy, non-invasive, fast, and cost-effective. Thus, different studies have explored the possibility of using salivary factors as biomarkers for the development and progression of OSCC and OPMDs [ 9 , 10 , 11 ]. The aim of this study was to perform an exploratory systematic review about the different salivary molecules that have been assessed as possible biomarkers for the diagnosis of OSCC.…”

Section: Introductionmentioning

confidence: 99%

Salivary Biomarkers for Oral Cancer Detection: An Exploratory Systematic Review

Bastías,

Maturana,

Marín

et al. 2024

IJMS

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Different efforts have been made to find better and less invasive methods for the diagnosis and prediction of oral cancer, such as the study of saliva as a source of biomarkers. The aim of this study was to perform a scoping review about salivary molecules that have been assessed as possible biomarkers for the diagnosis of oral squamous cell carcinoma (OSCC). A search was conducted using EBSCO, PubMed (MEDLINE), Scopus, and Web of Science. The research question was as follows: which molecules present in saliva have utility to be used as biomarkers for the early detection of oral cancer? Sixty-two studies were included. Over 100 molecules were assessed. Most of the markers were oriented towards the early diagnosis of OSCC and were classified based on their ability for detecting OSCC and oral potentially malignant disorders (OPMDs), OSCC outcome prediction, and the prediction of the malignant transformation of OPMDs. TNF-α, IL-1β, IL-6 IL-8, LDH, and MMP-9 were the most studied, with almost all studies reporting high sensitivity and specificity values. TNF-α, IL-1β, IL-6 IL-8, LDH, and MMP-9 are the most promising salivary biomarkers. However, more studies with larger cohorts are needed before translating the use of these biomarkers to clinical settings.

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IL-1/IL-1R Signaling in Head and Neck Cancer

Cited by 16 publications

References 170 publications

Aging and oral squamous cell carcinoma development: the role of cellular senescence

Aging and oral squamous cell carcinoma development: the role of cellular senescence

IL1 Pathway in HPV-Negative HNSCC Cells Is an Indicator of Radioresistance After Photon and Carbon Ion Irradiation Without Functional Involvement

Salivary Biomarkers for Oral Cancer Detection: An Exploratory Systematic Review

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