The expression and prognostic impact of proinflammatory cytokines and their associations with carcinogens in oropharyngeal squamous cell carcinoma

Lin, Chi-Maw; Lin, Long-Wei; Chen, Yawen; Ye, Yi-Ling

doi:10.1007/s00262-020-02488-w

Cited by 20 publications

(18 citation statements)

References 29 publications

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“…Finally, analyses of surgical specimens of oropharyngeal squamous cell carcinoma indicated that high IFN-γ and low IL-4, low TSLP, and low TGFβ expression was associated with better prognosis in oropharyngeal squamous cell carcinoma patients (48).…”

Section: Oropharyngeal Squamous Cell Carcinomamentioning

confidence: 97%

Thymic Stromal Lymphopoietin and Cancer: Th2-Dependent and -Independent Mechanisms

Protti

Monte

2020

Front. Immunol.

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The thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine originally cloned from a murine thymic stromal cell line, and subsequently a human homolog was identified using database search methods. Human TSLP is mostly expressed in epithelial cells, among which are keratinocytes as well as stromal cells such as fibroblasts and immune cells. Human TSLP was first described to activate myeloid dendritic cells, which prime naïve T helper cells to produce high concentrations of Th2 cytokines, thus representing a key cytokine in triggering dendritic cells-mediated allergic Th2 inflammation. TSLP and/or its receptor has been shown to be expressed in several tumor types, where TSLP expression is associated with functional activities that can be associated or not with the induction of a Th2-prone tumor microenvironment, i.e., Th2-dependent and Th2-independent mechanisms. These mechanisms involve tissue-and immune cell target-dependent tumor-promoting or tumor-suppressive functions in different or even the same tumor type. Here we report and discuss the Th2-dependent and Th2-independent roles of TSLP in cancer and possible therapeutic targeting.

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Section: Oropharyngeal Squamous Cell Carcinomamentioning

confidence: 97%

Thymic Stromal Lymphopoietin and Cancer: Th2-Dependent and -Independent Mechanisms

Protti

Monte

2020

Front. Immunol.

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“…Several genes in the immune genes model had been investigated in human cancers. Thymic stromal lymphopoietin (TSLP), a critical upstream cytokine inducing type 2 in ammation, represent a poor prognostic factor for oropharyngeal squamous cell carcinoma (OPSCC) (14). , an in ammatory cytokine that functions in in ammation and cancer, participate in a positive feedback loop that enhances invasion/migration ability in lung cancer (15).…”

Section: Discussionmentioning

confidence: 99%

Identification of an independent immune-genes prognostic index for breast cancer

Chen

Dong

Pan

et al. 2020

Preprint

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Objective Increasing evidence has indicated an association between immune micro-environment in breast cancer and clinical outcomes. The aim of this research is to comprehensively investigate the effect of tumor immune genes on the prognosis of breast cancer patients. Methods 2498 immune genes were downloaded from ImmPort database. Additionally, we identified and downloaded the transcriptome data of patients with breast cancer from the TCGA database through the R package, as well as relevant clinical information. Survival R package was applied in survival analyses for hub-genes. Cox regression analysis was used to analyze the effect of immune genes on the prognosis of breast cancer. Immune risk scoring model was constructed based on the statistical correlation between hub immune genes and survival. Meanwhile, multivariate cox regression analysis was utilized to investigate whether the immune genes risk score model was an independent factor for predicting the prognosis of breast cancer. Nomogram was constructed to comprehensively predict the survival rate of breast cancer. P < 0.05 was considered to be statistically significant. Results The results of the difference analysis showed that 556 immune genes exhibited differential expression between normal and breast cancer tissues (p < 0. 05). Univariate cox regression analysis revealed 66 immune genes statistically correlated with breast cancer related survival risk, of which 30 were associated with overall survival (P < 0.05). In addition, a 15-genes based immune genes risk scoring model was constructed through lasso COX regression analysis. KM curve indicated that patients in high-risk were associated with poor outcomes (p < 0.001). ROC curve indicated that the immune risk score model was reliable in predicting survival risk (5-year OS, AUC = 0.752). Our model showed satisfying AUC and survival correlation in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Furthermore, multivariate cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of breast cancer. A nomogram was established to comprehensively predict the survival of breast cancer patients with the results of multivariate cox regression analysis. Finally, we found that 15 immune genes and risk scores were significantly associated with clinical factors and prognosis, and were involved in multiple oncogenic pathways. Conclusion Collectively, tumor immune genes played an essential role in the prognosis of breast cancer. Furthermore, immune risk score was an independent predictive factor of breast cancer, indicating a poor survival.

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“…The inflammatory milieu of the TME plus the relative proportions of, e.g., T cell effector or suppressor cells populations are likely to influence the clinical outcomes of the patients. For example, studies have associated higher interferon gamma but lower interleukin-4 and transforming growth factor-beta levels in HPV-positive compared to HPV-negative OPSCC [ 58 ]. The presence in the TME of IFN-gamma-producing CD4+ and CD8+ T cells, inferred from expression of the transcription factor Tbet, has shown association with improved OS [ 45 , 59 ], while the presence of non-T cell IL-17-producing cells was linked to poorer survival [ 60 ].…”

Section: Immune Infiltration Of Opsccmentioning

confidence: 99%

Oropharyngeal Squamous Cell Carcinoma Treatment in the Era of Immune Checkpoint Inhibitors

Stern

Dalianis

2021

Viruses

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While head and neck squamous cell carcinomas (HNSCC) are marginally decreasing due to the reduction in exposure to the major risk factors, tobacco and alcohol, the incidence of high-risk human papillomavirus (HPV)-positive oropharynx squamous cell carcinomas (OPSCC), especially those in the tonsil and base of tongue subsites, are increasing. Patients with the latter are younger, display a longer overall survival, and show a lower recurrence rate after standard-of-care treatment than those with HPV-negative OPSCC. This may reflect an important role for immune surveillance and control during the natural history of the virally driven tumour development. Immune deviation through acquisition of immune-suppressive factors in the tumour microenvironment (TME) is discussed in relation to treatment response. Understanding how the different immune factors are integrated in the TME battleground offers opportunities for identifying prognostic biomarkers as well as novel therapeutic strategies. OPSCC generally receive surgery or radiotherapy for early-stage tumour treatment, but many patients present with locoregionally advanced disease requiring multimodality therapies which can involve considerable complications. This review focuses on the utilization of newly emerged immune checkpoint inhibitors (PD-1/PD-L1 pathway) for treatment of HNSCC, in particular HPV-positive OPSCC, since they could be less toxic and more efficacious. PD-1/PD-L1 expression in the TME has been extensively investigated as a biomarker of patient response but is yet to provide a really effective means for stratification of treatment. Extensive testing of combinations of therapeutic approaches by types and sequencing will fuel the next evolution of treatment for OPSCC.

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The expression and prognostic impact of proinflammatory cytokines and their associations with carcinogens in oropharyngeal squamous cell carcinoma

Cited by 20 publications

References 29 publications

Thymic Stromal Lymphopoietin and Cancer: Th2-Dependent and -Independent Mechanisms

Thymic Stromal Lymphopoietin and Cancer: Th2-Dependent and -Independent Mechanisms

Identification of an independent immune-genes prognostic index for breast cancer

Oropharyngeal Squamous Cell Carcinoma Treatment in the Era of Immune Checkpoint Inhibitors

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