Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area

Muraro, Elena; Vaccher, Emanuela; Furlan, Carlo; Fratta, Elisabetta; Fanetti, Giuseppe; Faè, Damiana Antonia; Martorelli, Debora; Cangemi, Michela; Polesel, Jerry; Navarria, F. L.; Gobitti, Carlo; Comaro, Elisa; Scaini, Chiara; Pratesi, Chiara; Zanussi, Stefania; Lupato, Valentina; Grando, Giuseppe; Giacomarra, Vittorio; Sulfaro, Sandro; Barzan, Luigi; Dolcetti, Riccardo; Steffan, Agostino; Canzonieri, Vincenzo; Franchin, Giovanni

doi:10.1007/s12253-020-00859-3

Cited by 5 publications

(6 citation statements)

References 42 publications

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“…Studies have shown that high levels of CD3 + cells cells are associated with a favorable OS [ 17 ]. CD8 + T-activatable effector cells are cytotoxic T cells [ 18 ], and previous studies have detected CD8 + cells in NPC microenvironments, which can predict treatment effectiveness [ 19 ]. CD4 + cells and CD8 + cells are important components of T lymphocyte immune regulation.…”

Section: Discussionmentioning

confidence: 99%

Effect of immune-modulating metronomic capecitabine as an adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma

He,

Luo,

Liu

et al. 2024

BMC Immunol

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Introduction Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy. Aim We aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC. Subjects and methods 28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups. Results The median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P < 0.05). The CD4/CD8 ratio and proportion of monocyte-derived dendritic cells were also higher in the experimental group than in the control group, but the difference was not statistically significant (P ≥ 0.05). Comparisons of 3-year overall survival, local-regional recurrence-free survival, progression-free survival, and distant metastasis-free survival between the two groups showed percentages of 92.9% vs. 78.6%, 92.9% vs. 92.9%, 78.6% vs. 71.4%, and 85.7% vs. 0.78 0.6% respectively, but these differences were not significant (P > 0 0.05 ). Conclusion Metronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC. Trial registration NCT02958111, date of registration 04-11-2016.

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Section: Discussionmentioning

confidence: 99%

Effect of immune-modulating metronomic capecitabine as an adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma

He,

Luo,

Liu

et al. 2024

BMC Immunol

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“…Lines of evidences revealed the potential of aberration FOXP3 methylation for biomarker applications, such as identifying the severity of autoimmune diseases, 19 predicting acute rejection after organ transplantation, 30 and assessing tumor prognosis and efficacy of therapies. 20 However, the application of epigenetic markers has limitations in terms of the compatibility of influencing factors and the accurate prediction of individual risk. The nomogram has been considered as a reliable tool to accurately quantify the individual risk through a comprehensive assessment of the contribution of influencing factors to adverse outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…17 Anomalous DNA methylation of FOXP3, which plays an important role in inhibiting FOXP3 expression and subsequent immunosuppressive dysfunction, has been considered to be a critical marker for identifying the risk of poor prognosis in immunerelated diseases such as autoimmune diseases and tumors. [18][19][20] Our previous studies demonstrated that the aberration of FOXP3 methylation could be sustained following continued exposure to arsenic and was involved in arsenic poisoning by triggering inflammation. 21,22 These results suggest that FOXP3 methylation might be an early epigenetic biomarker of arsenic poisoning, but it is unknown whether FOXP3 methylation exhibits accuracy, sensitivity and reliability in prediction of arsenic poisoning risk.…”

Section: Introductionmentioning

confidence: 99%

The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk

Fang

Zhang

2022

Hum Exp Toxicol

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Background and Purpose: Arsenic exposure can lead to skin lesions and multiple organ damage, which are not easily reversible and for which there is no effective therapeutics. Identification of reliable epigenetic markers is essential for early recognition of arsenic poisoning risk. Anomalous DNA methylation of immune homeostasis regulator FOXP3 is a critical mechanism for triggering arsenic poisoning. This study aims to explore the value of FOXP3 methylation in the identification of arsenic poisoning risk. Methods: 88 arsenic poisoning subjects and 41 references were recruited. Urinary arsenic contents and FOXP3 methylation in PBLCs was measured by ICP-MS and pyrosequencing, respectively. Results: The results showed that the elevated FOXP3 methylation in PBLCs were associated with the increased levels of urinary arsenic and were positively associated with the increased risk of arsenic poisoning and its progression. The result of mediation analysis revealed that 24.3% of the effect of arsenic exposure on the risk of arsenic poisoning was mediated by increased FOXP3 methylation. Additionally, we constructed a nomogram model with FOXP3 methylation as an epigenetic predictor to assess the probability of individual arsenic poisoning. The model showed a robust ability in the discrimination of arsenic poisoning risk, with an area under receiver operating characteristics curve of 0.897(0.845–0.949) and more than 70% accuracy. The calibration curves and the Harrell concordance index showed that the consistency rate between the probability predicted by the nomogram model and the actual probability is 89.7%. Conclusions: Taken together, we found the great potential of FOXP3 methylation for the identification of arsenic poisoning risk and provided a new approach to the application of epigenetic markers in accurately quantifying the risk of adverse outcomes.

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“…On the contrary, the removal of the methyl group is catalyzed by the ten-eleven translocation (TET) family triggered by either active or passive mechanisms, known as the synergistic activation with the thymine DNA glycosylase (TDG) and the base-excision repair (BER) machinery [ 29 , 30 ] or the DNA replication-dependent passive pathway [ 31 ], respectively. Therefore, as one of the most common epigenetic regulations, DNA methylation on both global and specific sites has been broadly considered as the promising biomarkers to forecast tumor phenotypes or overall survival or patient prognosis [ 32 – 38 ].…”

Section: Fundamental Modes Of Epigeneticsmentioning

confidence: 99%

Epigenetic regulation and therapeutic targets in the tumor microenvironment

et al. 2023

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The tumor microenvironment (TME) is crucial to neoplastic processes, fostering proliferation, angiogenesis and metastasis. Epigenetic regulations, primarily including DNA and RNA methylation, histone modification and non-coding RNA, have been generally recognized as an essential feature of tumor malignancy, exceedingly contributing to the dysregulation of the core gene expression in neoplastic cells, bringing about the evasion of immunosurveillance by influencing the immune cells in TME. Recently, compelling evidence have highlighted that clinical therapeutic approaches based on epigenetic machinery modulate carcinogenesis through targeting TME components, including normalizing cells’ phenotype, suppressing cells’ neovascularization and repressing the immunosuppressive components in TME. Therefore, TME components have been nominated as a promising target for epigenetic drugs in clinical cancer management. This review focuses on the mechanisms of epigenetic modifications occurring to the pivotal TME components including the stroma, immune and myeloid cells in various tumors reported in the last five years, concludes the tight correlation between TME reprogramming and tumor progression and immunosuppression, summarizes the current advances in cancer clinical treatments and potential therapeutic targets with reference to epigenetic drugs. Finally, we summarize some of the restrictions in the field of cancer research at the moment, further discuss several interesting epigenetic gene targets with potential strategies to boost antitumor immunity.

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Predictive Value of CD8 Expression and FoxP3 Methylation in Nasopharyngeal Carcinoma Patients Treated with Chemoradiotherapy in a Non-endemic Area

Cited by 5 publications

References 42 publications

Effect of immune-modulating metronomic capecitabine as an adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma

Effect of immune-modulating metronomic capecitabine as an adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma

The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk

Epigenetic regulation and therapeutic targets in the tumor microenvironment

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