Intratumoral IFN-α gene delivery reduces tumor-infiltrating regulatory T cells through the downregulation of tumor CCL17 expression

Hirata, Aya; Hashimoto, Hisayoshi; Shibasaki, Chihiro; Narumi, Kenta; Aoki, Kazunori

doi:10.1038/s41417-018-0059-5

Cited by 35 publications

(27 citation statements)

References 32 publications

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“…CCR4 blockade inhibited tumour growth and Tregs infiltration into tissues with improved survival and a low incidence of clinically relevant toxicity [ 158 ]. Additionally, intratumoural IFN-α gene delivery reduced the trafficking of Tregs to the tumour through the downregulation of tumour CCL17 expression [ 159 ]. CCL22 expression by DCs promotes the formation of cell–cell contacts and interaction with Tregs through receptor CCR4.…”

Section: Tumour Immunotherapy Strategies Targeting Tregsmentioning

confidence: 99%

Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects

et al. 2020

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Regulatory T cells (Tregs) characterized by the expression of the master transcription factor forkhead box protein p3 (Foxp3) suppress anticancer immunity, thereby hindering protective immunosurveillance of tumours and hampering effective antitumour immune responses in tumour-bearing hosts, constitute a current research hotspot in the field. However, Tregs are also essential for the maintenance of the immune tolerance of the body and share many molecular signalling pathways with conventional T cells, including cytotoxic T cells, the primary mediators of tumour immunity. Hence, the inability to specifically target and neutralize Tregs in the tumour microenvironment without globally compromising self-tolerance poses a significant challenge. Here, we review recent advances in characterizing tumour-infiltrating Tregs with a focus on the functional roles of costimulatory and inhibitory receptors in Tregs, evaluate their potential as clinical targets, and systematically summarize their roles in potential treatment strategies. Also, we propose modalities to integrate our increasing knowledge on Tregs phenotype and function for the rational design of checkpoint inhibitor-based combination therapies. Finally, we propose possible treatment strategies that can be used to develop Treg-targeted therapies.

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Section: Tumour Immunotherapy Strategies Targeting Tregsmentioning

confidence: 99%

Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects

et al. 2020

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“…CCL17 is a lymphocyte chemokine that plays an important role in the transport and activation of T cells. Tumor-associated neutrophils released cytokine CCL17 , which can recruit Treg cells into the tumor microenvironment to affect antitumor immunity ( 35 , 36 ). The overexpression of APOL1 and CCL17 in EEA may also improve the prognosis of patients by enhancing these specific functions.…”

Section: Discussionmentioning

confidence: 99%

Screening and Identification of Prognostic Tumor-Infiltrating Immune Cells and Genes of Endometrioid Endometrial Adenocarcinoma: Based on The Cancer Genome Atlas Database and Bioinformatics

Chen

Wang

et al. 2020

Front. Oncol.

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BackgroundEndometrioid endometrial adenocarcinoma (EEA) is one of the most common tumors in the female reproductive system. With the further understanding of immune regulation mechanism in tumor microenvironment, immunotherapy is emerging in tumor treatment. However, there are few systematic studies on EEA immune infiltration.MethodsIn this study, prognostic tumor-infiltrating immune cells (TIICs) and related genes of EEA were comprehensively analyzed for the first time through the bioinformatics method with CIBERSORT algorithm as the core. Gene expression profile data were downloaded from the TCGA database, and the abundance ratio of TIICs was obtained. Kaplan–Meier analysis and Cox regression analysis were used to identify prognostic TIICs. EEA samples were grouped according to the risk score in Cox regression model. Differential analysis and functional enrichment analyses were performed on high- and low-risk groups to find survival-related hub genes, which were verified by Tumor Immune Estimation Resource (TIMER).ResultFour TIICs including memory CD4+ T cells, regulatory T cells, natural killer cells and dendritic cells were identified. And two hub gene modules were found, in which six hub genes including APOL1, CCL17, RBP4, KRT15, KRT71, and KRT79 were significantly related to overall survival and were closely correlated with some certain TIICs in the validation of TIMER.ConclusionIn this study, four prognostic TIICs and six hub genes were found to be closely related to EEA. These findings provided new potential targets for EEA immunotherapy.

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“…Some previous researches have revealed the association between the 6 genes we identi ed with some other cancer pathogenesis. It was reported that CCL17 played a critical role in preventing tumorigenesis for its ability to engage CCR4+CD8+ T cells [22][23][24]. Okada et al used RGD-ber-mutant adenoviral vector transfected into the tumors of melanomabearing mice, and found that recombinant AdRGD-CCL17 induced CD8+CTL cell aggregation to tumor tissue, which effectively inhibiting tumor growth [25].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Six-gene Signature Predicting Overall Survival for Cervical Cancer

Sun

Zhou

Peng

et al. 2020

Preprint

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Background: Although the incidence of cervical cancer has decreased in decades with the development of human papillomavirus vaccines and cancer screening, cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Identify the potential biomarker for treatment and prognosis of cervical cancer is necessary.Methods: Samples with mRNA-seq, copy number variant, single single nucleotide polymorphism data and clinical follow-up information were download from TCGA database, which were randomly divided into training datasets (N=146) and test datasets (N=147). We selected and identified prognostic gene set and genomic mutated gene set and then integrated the two set of data with random survival forest algorithm and constructed a prognostic signature. External validation datasets and immunohistochemical staining were also evaluated.Results: We obtained 1,416 different expression prognostic-related genes, 624 genes with copy number amplification, 1,038 genes with copy number deletion, and 163 significantly mutated gene. A total of 75 candidate genes were obtained after overlap of the different expression genes and genomic variations. Subsequently we obtained six characteristic genes through random survival forest algorithm. The results showed that high expression of SLC19A3, FURIN, SLC22A3, DPAGT1 and low expression of CCL17, DES were associated with poor prognosis in cervical cancer patients. We constructed a six-gene signature which can separate cervical cancer samples associated with different overall survival and showed robust performance for predicting survival (Training set: p ˂ 0.001, AUC = 0.82; Testing set: p ˂ 0.01, AUC = 0.59). Conclusions: Our study identified a novel six-gene signature and nomogram to predict overall survival of cervical cancer, which may be beneficial to clinical decision making for individual treatment.

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Intratumoral IFN-α gene delivery reduces tumor-infiltrating regulatory T cells through the downregulation of tumor CCL17 expression

Cited by 35 publications

References 32 publications

Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects

Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects

Screening and Identification of Prognostic Tumor-Infiltrating Immune Cells and Genes of Endometrioid Endometrial Adenocarcinoma: Based on The Cancer Genome Atlas Database and Bioinformatics

Identification of a Six-gene Signature Predicting Overall Survival for Cervical Cancer

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