Human FOXP3 and tumour microenvironment

Wang, Jia; Gong, Ruining; Zhao, Chenyang; Lei, Ke; Sun, Xiankai; Ren, He

doi:10.1111/imm.13520

Cited by 54 publications

(33 citation statements)

References 77 publications

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“…A previous study found SLFN5 co-localization with T cells and M2-type macrophages in precancerous lesions of GC, implying that SLFN5 plays an immunosuppressive role in GC (23). Consistently, we found that SLFN5 is primarily expressed in Treg and naïve T cells, which play a tumor-promoting role in cancer (47). Similarly, high SLFN11 expression in breast cancer is related to more aggressive and immune-activated tumors, whereas low SLFN11 expression is associated with low aggressiveness and low immune activation status (48).…”

Section: Discussionsupporting

confidence: 75%

Schlafen family is a prognostic biomarker and corresponds with immune infiltration in gastric cancer

Chen

Liang

et al. 2022

Front. Immunol.

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The Schlafen (SLFN) gene family plays an important role in immune cell differentiation and immune regulation. Previous studies have found that the increased SLFN5 expression in patients with intestinal metaplasia correlates with gastric cancer (GC) progression. However, no investigation has been conducted on the SLFN family in GC. Therefore, we systematically explore the expression and prognostic value of SLFN family members in patients with GC, elucidating their possible biological function and its correlation with tumor immune cells infiltration. TCGA database results indicated that the SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN13 expression was significantly higher in GC. The UALCAN and KM plotter databases indicated that enhanced the SLFN family expression was associated with lymph node metastasis, tumor stage, and tumor grade and predicted an adverse prognosis. cBioportal database revealed that the SLFN family had a high frequency of genetic alterations in GC (about 12%), including mutations and amplification. The GeneMANIA and STRING databases identified 20 interacting genes and 16 interacting proteins that act as potential targets of the SLFN family. SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 may be implicated in the immunological response, according to Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, Timer and TISIDB databases indicate that SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 are involved in the immune response. Furthermore, Timer, TCGA, and TISIDB databases suggested that the SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 expression in GC is highly linked with immune cell infiltration levels, immune checkpoint, and the many immune cell marker sets expression. We isolated three samples of peripheral blood mononuclear cell (PBMC) and activated T cells; the results showed the expression of SLFN family members decreased significantly when T cell active. In conclusion, the SLFN family of proteins may act as a prognostic indicator of GC and is associated with immune cell infiltration and immune checkpoint expression in GC. Additionally, it may be involved in tumor immune evasion by regulating T cell activation.

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Section: Discussionsupporting

confidence: 75%

Schlafen family is a prognostic biomarker and corresponds with immune infiltration in gastric cancer

Chen

Liang

et al. 2022

Front. Immunol.

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“…FoxP3 regulatory T cells are an immunosuppressive subpopulation of CD4+ T cells that modulate the anti-tumor response mediated by CD8+ T cells. In the TIME, high levels of Tregs are frequently presented and their main effect is to create and maintain an immune tolerant environment [ 69 ]. 15 studies measured Tregs using the FoxP3 marker (46.8%) [ 28 – 31 , 35 , 37 , 42 , 58 , 59 , 64 – 67 , 70 , 71 ].…”

Section: Macrophagesmentioning

confidence: 99%

Effect of neoadjuvant chemotherapy on tumor immune infiltration in breast cancer patients: Systematic review and meta-analysis

et al. 2023

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The tumor immune infiltrate has an impact on cancer control and progression, additionally a growing body of evidence has proposed the role of neoadjuvant chemotherapy in modulating the contexture of the tumor immune infiltrate. Here, we performed a systematic review to evaluate the effect of chemotherapy in the immune infiltration of breast cancer tumors. We systematically searched Pubmed/MEDLINE, EMBASE, CENTRAL, and BVS databases with a cutoff date of 11/06/2022. Studies in patients with pathological diagnosis of BC, whose first line of treatment was only NAC, were included. Only published experimental studies that measured tumor immune infiltrate before and after NAC by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHQ), or transcriptome were included. Reviews, studies with animal models and in-vitro models were excluded. Studies in which BC was not the primary tumor or studies with patients who received other types of neoadjuvant therapy were also excluded. The NIH quality assessment tool for before and after studies without control was used. We included 32 articles that evaluated the proximal tumor microenvironment before and after neoadjuvant chemotherapy in 2072 patients who received NAC as first line of treatment and who were evaluated for immune infiltrate in the pre- and post-chemotherapy tumor sample. Results were divided into two major categories immune cells and in-situ expression of immune checkpoints and cytokines. Qualitative synthesis was performed with the 32 articles included, and in nine of them a quantitative analysis was achieved, resulting in six meta-analyses. Despite high heterogeneity among the articles regarding treatment received, type of tumor reported, and techniques used to evaluate immune infiltrate, we found a significant decrease of TILs and FoxP3 expression after neoadjuvant chemotherapy. The study protocol was registered in PROSPERO 2021 (Protocol ID: CRD42021243784) on 6/29/2021.

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“…The upstream regulatory genes, the related signaling pathways, and the epigenetic changes of FOXP3 in tumors have not been fully elucidated. Meanwhile, both FOXP3 + Tregs and tumor-derived FOXP3 are expressed in TME [ 72 ], due to the complexity between the cross-talk of FOXP3 + Tregs and FOXP3 + tumor cells, and it is necessary to further study the performance of communication mechanisms and their effect on tumor biological behaviors.…”

Section: Limitations and Deficienciesmentioning

confidence: 99%

The Role of FOXP3 on Tumor Metastasis and Its Interaction with Traditional Chinese Medicine

Miao

Xiao

et al. 2022

Molecules

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Forkhead box protein 3 (FOXP3) is an important transcription factor for regulatory T cells (Tregs) and plays an important role in their immunosuppressive function. In recent years, studies have found that FOXP3 is expressed in many kinds of tumors and plays different roles in tumors’ biological behaviors, including tumor proliferation, metastasis, drug resistance, and prognosis. However, the effects of FOXP3 on tumor metastasis and its interaction with traditional Chinese medicine (TCM) remain unclear. Therefore, in this review, we focus on the effects of FOXP3 on tumor metastasis and its relationship with TCM, which can provide evidence for further research and therapy in clinical settings.

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Human FOXP3 and tumour microenvironment

Cited by 54 publications

References 77 publications

Schlafen family is a prognostic biomarker and corresponds with immune infiltration in gastric cancer

Schlafen family is a prognostic biomarker and corresponds with immune infiltration in gastric cancer

Effect of neoadjuvant chemotherapy on tumor immune infiltration in breast cancer patients: Systematic review and meta-analysis

The Role of FOXP3 on Tumor Metastasis and Its Interaction with Traditional Chinese Medicine

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