Potential biomarkers for radiosensitivity in head and neck cancers

Pardo-Reoyo, Sherly; Roig-Lopez, J. L.; Yang, Eddy S.

doi:10.21037/atm.2016.12.45

Cited by 8 publications

(10 citation statements)

References 33 publications

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“…Identification of deregulated proteins could be applied clinically in terms of either radioresistance-associated biomarkers or as potential targets for radiosensitization. These novel biomarkers related to either radiosensitivity or radioresistance would permit improved stratification of HNSCC patients based on the predicted response to irradiation [69]. Radiosensitization of more radioresistant tumors could also lead to reduced total irradiation dose, fewer and/or milder adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of different response to ionizing irradiation in isogenic head and neck cancer cell lines

et al. 2019

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Background: Treatment options for recurrent head and neck tumours in the previously irradiated area are limited, including re-irradiation due to radioresistance of the recurrent tumour and previous dose received by surrounding normal tissues. As an in vitro model to study radioresistance mechanisms, isogenic cells with different radiosensitivity can be used. However, they are not readily available. Therefore, our objective was to establish and characterize radioresistant isogenic human pharyngeal squamous carcinoma cells and to evaluate early radiation response in isogenic parental, radioresistant and radiosensitive cells. Methods: Radioresistant cells were derived from parental FaDu cells by repeated exposure to ionizing radiation. Radiosensitivity of the established isogenic radioresistant FaDu-RR cells was evaluated by clonogenic assay and compared to isogenic parental FaDu and radiosensitive 2A3 cells. Additional phenotypic characterization of these isogenic cells with different radiosensitivity included evaluation of chemosensitivity, cell proliferation, cell cycle, radiation-induced apoptosis, resolution of DNA double-strand breaks, and DNA damage and repair signalling gene expression before and after irradiation. Results: In the newly established radioresistant cells in response to 5 Gy irradiation, we observed no alteration in cell cycle regulation, but delayed induction and enhanced resolution of DNA double-strand breaks, lower induction of apoptosis, and pronounced over-expression of DNA damage signalling genes in comparison to parental cells. On the other hand, radiosensitive 2A3 cells were arrested in G 2 /M-phase in response to 5 Gy irradiation, had a prominent accumulation of and slower resolution of DNA double-strand breaks, and no change in DNA damage signalling genes expression. Conclusions: We concluded that the emergence of the radioresistance in the established radioresistant isogenic cells can be at least partially attributed to the enhanced DNA double-strand break repair, altered expression of DNA damage signalling and repair genes. On the other hand, in radiosensitive isogenic cells the reduced ability to repair a high number of induced DNA double-strand breaks and no transcriptional response in DNA damage signalling genes indicate on a lack of adaptive response to irradiation. Altogether, our results confirmed that these isogenic cells with different radiosensitivity are an appropriate model to study the mechanisms of radioresistance.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of different response to ionizing irradiation in isogenic head and neck cancer cell lines

et al. 2019

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“…Recent studies reported that various immune parameters are related to radiosensitivity, and that the CD8 + T cell or Treg population plays an important role in the antitumor effect of RT 28‐31,37 . In the present study, we investigated the association between LC and TIL status, PD‐L1 expression, and their combination on the tumor radiosensitivity of 91 patients with SCC‐L who had undergone a definitive RT.…”

Section: Discussionmentioning

confidence: 94%

“…Recent studies reported that various immune parameters are related to radiosensitivity, and that the CD8 + T cell or Treg population plays an important role in the antitumor effect of RT. [28][29][30][31]37 In the present study, we investigated the association between LC and TIL status, PD-L1 expression, and their combination on the tumor radiosensitivity of 91 patients with SCC-L who had undergone a definitive RT. Using multivariate analysis, we found that CD8/FOXP3 ratio, but not CD8+, CD4+, nor FOXP3 TIL density; PD-L1 expression; and CD8/CD4 ratio showed significant association with LC.…”

Section: Discussionmentioning

confidence: 99%

“…8,27 Although several studies have reported the association between radiosensitivity and several predictive biomarkers in patients with HNC, limited information is available regarding the association between radiosensitivity and the tumor immune microenvironment (TIM). [28][29][30][31][32] Therefore, the present study aimed to assess the combined effect of the ratio of preexisting T cell subpopulations in the TIM and the expression of PD-L1 on tumor cells on LC in the irradiated fields after RT in patients with squamous cell carcinoma of the larynx (SCC-L).…”

Section: Introductionmentioning

confidence: 99%

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Predictive value of CD8/FOXP3 ratio combined with PD‐L1 expression for radiosensitivity in patients with squamous cell carcinoma of the larynx receiving definitive radiation therapy

et al. 2020

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Background: Little is known about immune-related radiosensitivity in patients with squamous cell carcinoma of the larynx (SCC-L) treated with radiation therapy (RT). Methods: We retrospectively reviewed 91 patients with SCC-L treated with RT or chemoradiation therapy and performed immunohistochemical examination to analyze PD-L1 level on tumor cells, CD4 + tumor-infiltrating lymphocytes (TILs), CD8 + TIL, and FOXP3 + TIL using pretreated biopsy specimens. The association between these immune-related parameters and radiosensitivity was evaluated. Results: Multivariate analyses showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression was an independent and significant favorable predictive factor for local control, compared with the other groups. Conclusions: We showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression might be a useful biomarker of radiosensitivity in patients with SCC-L receiving definitive RT. We propose that coassessment of CD8/FOXP3 ratio and PD-L1 expression level in tumor cells can help predict potential radiosensitivity in patients with SCC-L.

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“…Tumor radiosensitivity may also influence the effect of TTI on outcome. While to some extent it may be evaluated before RT begins (e.g., by molecular profiling, identification of hypoxic cells, and the determination of HPV status in oropharyngeal primary tumors), in daily clinical practice it is usually not considered when planning treatment [45,46]. In order to diminish the impact of intrinsic tumor radiosensitivity, the patients in our study with residual disease at 10-12 weeks post-RT were excluded from the analysis of LRC.…”

Section: Discussionmentioning

confidence: 99%

Impact of delays in radiotherapy of head and neck cancer on outcome

et al. 2020

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Background: In head and neck cancer (HNC), the relationship between a delay in starting radiotherapy (RT) and the outcome is unclear. The aim of the present study was to determine the impact of the amount of time before treatment intervention (TTI) and the growth kinetics of individual tumors on treatment outcomes and survival. Methods: Two hundred sixty-two HNC patients with 273 primary tumors, treated with definitive (chemo) RT, were retrospectively analyzed. The TTI was defined as the time interval between the date of histopathologic diagnosis and the first day of the RT course. Volumetric data on 57 tumors were obtained from diagnostic and RT planning computer tomography (CT) scans in order to calculate the tumor growth kinetic parameters. Results: No significant association between locoregional control or cause-specific hazards and TTI was found. The log hazard for locoregional recurrence linearly increased during the first 40 days of waiting for RT, although this was not significant. The median tumor volume relative increase rate and tumor volume doubling time was 3.2%/day and 19 days, respectively, and neither had any impact on locoregional control or cause-specific hazards. Conclusion: The association between a delay in starting RT and the outcome is complex and does not harm all patients waiting for RT. Further research into imaging-derived kinetic data on individual tumors is warranted in order to identify patients at an increased risk of adverse outcomes due to a delay in starting RT.

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Potential biomarkers for radiosensitivity in head and neck cancers

Cited by 8 publications

References 33 publications

Mechanisms of different response to ionizing irradiation in isogenic head and neck cancer cell lines

Mechanisms of different response to ionizing irradiation in isogenic head and neck cancer cell lines

Predictive value of CD8/FOXP3 ratio combined with PD‐L1 expression for radiosensitivity in patients with squamous cell carcinoma of the larynx receiving definitive radiation therapy

Impact of delays in radiotherapy of head and neck cancer on outcome

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