Regulatory T cells: Their role in triple‐negative breast cancer progression and metastasis

Malla, Rama Rao; Padmaraju, Vasudevaraju; Vempati, Rahul Kumar; Marni, Rakshmitha; Merchant, Neha; Nagaraju, Ganji Purnachandra

doi:10.1002/cncr.34084

Cited by 26 publications

(17 citation statements)

References 86 publications

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“…Consistent with previous demonstrations ( 8 , 10 ), the survival analysis in TNBC suggests that high Treg expression indicates worse prognosis. We subsequently identified DEGs among the Treg-H and Treg-L groups, and the expression levels of immune-related genes and specific biomarkers of Tregs, such as CD4, FOXP3, and CD25, showed significant differences between the two groups, supporting the distinct TME between the Treg-H and Treg-L groups.…”

Section: Discussionsupporting

confidence: 90%

“…Regulatory T cells (Tregs), a specialized subset of T cells that express CD4, CD25 and forkhead box protein P3 (FOXP3), act as key mediators of immunologic tolerance. In particular, Tregs obtain an immunosuppressive capacity after exposure to inflammatory conditions in the tumor microenvironment (TME), which then suppress autoimmunity by inhibiting T cell proliferation and cytokine production ( 8 – 10 ). Additionally, the depletion of Tregs could inhibit tumor growth ( 11 , 12 ), suggesting the promoting role of Tregs in TNBC progression.…”

Section: Introductionmentioning

confidence: 99%

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3D Collagen Fiber Concentration Regulates Treg Cell Infiltration in Triple Negative Breast Cancer

et al. 2022

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BackgroundTriple negative breast cancer (TNBC) is characterized by poor prognosis and a lack of effective therapeutic agents owing to the absence of biomarkers. A high abundance of tumor-infiltrating regulatory T cells (Tregs) was associated with worse prognosis in malignant disease. Exploring the association between Treg cell infiltration and TNBC will provide new insights for understanding TNBC immunosuppression and may pave the way for developing novel immune-based treatments.Materials and MethodsPatients from TCGA were divided into Treg-high (Treg-H) and Treg-low (Treg-L) groups based on the abundance of Tregs according to CIBERSORT analysis. The association between expression level of Tregs and the clinical characteristics as well as prognosis of breast cancer were evaluated. Next, a Treg-related prognostic model was established after survival-dependent univariate Cox and LASSO regression analysis, companied with an external GEO cohort validation. Then, GO, KEGG and GSEA analyses were performed between the Treg-H and Treg-L groups. Masson and Sirius red/Fast Green staining were applied for ECM characterization. Accordingly, Jurkat T cells were encapsulated in 3D collagen to mimic the ECM microenvironment, and the expression levels of CD4, FOXP3 and CD25 were quantified according to immunofluorescence staining.ResultsThe expression level of Tregs is significantly associated with the clinical characteristics of breast cancer patients, and a high level of Treg cell expression indicates a poor prognosis in TNBC. To further evaluate this, a Treg-related prognostic model was established that accurately predicted outcomes in both TCGA training and GEO validation cohorts of TNBC patients. Subsequently, ECM-associated signaling pathways were identified between the Treg-H and Treg-L groups, indicating the role of ECM in Treg infiltration. Since we found increasing collagen concentrations in TNBC patients with distant migration, we encapsulated Jurkat T cells within a 3D matrix with different collagen concentrations and observed that increasing collagen concentrations promoted the expression of Treg biomarkers, supporting the regulatory role of ECM in Treg infiltration.ConclusionOur results support the association between Treg expression and breast cancer progression as well as prognosis in the TNBC subtype. Moreover, increasing collagen density may promote Treg infiltration, and thus induce an immunosuppressed TME.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

3D Collagen Fiber Concentration Regulates Treg Cell Infiltration in Triple Negative Breast Cancer

et al. 2022

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“…In order to identify the T cell subsets associated with COL11A1, we further compared the correlation between the signature biomarkers of each T cell subsets and COL11A1 expression (Supplementary Table S2). It is not difficult to find that biomarkers such as Effector T-cell, Naïve T -cell, Effector Memory T-cell and Resident Memory T-cell related to tumor immunity in T cell subsets are negatively correlated with COL11A1 expression while the infiltration level of Treg and Resting Treg Malla et al, 2022) that have been previously confirmed by a large number of literatures to have tumor immunosuppressive effect and participate in tumor progression, were positively correlated with COL11A1 expression. In addition, we unexpectedly found a positive correlation between COL11A1 and the expression of PD-1, PD-L1 and CTLA-4 (Figure 6D).…”

Section: Discussionmentioning

confidence: 91%

COL11A1 serves as a biomarker for poor prognosis and correlates with immune infiltration in breast cancer

Luo

et al. 2022

Front. Genet.

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Breast cancer is the malignant tumor with the highest incidence rate at present, and its incidence rate ranks first in the female population. COL11A1 is an important component of collagen XI and is considered to play an important role in a variety of connective tissue diseases. Recent studies have shown that COL11A1 is associated with the occurrence and development of many kinds of malignant tumors. However, its prognostic value in breast cancer and its correlation with immune cell infiltration in tumor tissue are not clear. In this paper, we reveal the prognostic value of COL11A1 in breast cancer and its tumor immune-related function through in-depth bioinformatics analysis. The expression of COL11A1 is abnormally upregulated in breast cancer and is significantly related to the poor prognosis of breast cancer. In the analysis of the clinical characteristics of the patients, we found that the expression level of COLL11A1 was closely related to lymph node metastasis, PAM50 (Prediction Analysis of Microarray 50) expression, clinical stage and so on. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) all suggest that COL11A1 is related to tumor immunity. Further study found that the COL11A1 expression was significantly correlated with the degree of immune infiltration and the expression of a variety of immune cell markers in tumor tissue. More importantly, COL11A1 can affect the prognosis of breast cancer patients by participating in the regulation of tumor immune infiltration. Therefore, we believe that COL11A1 is a very potential target for diagnosis and treatment of breast cancer.

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“…These cells are reprogrammed to proliferate and differentiate, which in turn changes the transcription profiles of infiltrating immune cells and support immune evasion. Moreover, a high abundance of regulatory T cells is significantly associated with high tumor expression levels of immune checkpoint inhibitor genes ( 44 , 45 ), which may explain the effective response of the low CRG_score group to immunotherapy. Although the presence of B cells and plasma cells is a good predictor of patient prognosis ( 46 , 47 ), B cells also have immunosuppressive roles in TNBC by enhancing the levels of myeloid-derived suppressor cells (MDSCs) or promoting IL-10 levels to facilitate isotype conversion to immunosuppressive IgG4 antibodies ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic analysis of cuproptosis-related gene in triple-negative breast cancer

Sha

et al. 2022

Front. Immunol.

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BackgroundCuproptosis is a copper-dependent cell death mechanism that is associated with tumor progression, prognosis, and immune response. However, the potential role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) remains unclear.Patients and methodsIn total, 346 TNBC samples were collected from The Cancer Genome Atlas database and three Gene Expression Omnibus datasets, and were classified using R software packages. The relationships between the different subgroups and clinical pathological characteristics, immune infiltration characteristics, and mutation status of the TME were examined. Finally, a nomogram and calibration curve were constructed to predict patient survival probability to improve the clinical applicability of the CRG_score.ResultsWe identified two CRG clusters with immune cell infiltration characteristics highly consistent with those of the immune-inflamed and immune-desert clusters. Furthermore, we demonstrated that the gene signature can be used to evaluate tumor immune cell infiltration, clinical features, and prognostic status. Low CRG_scores were characterized by high tumor mutation burden and immune activation, good survival probability, and more immunoreactivity to CTLA4, while high CRG_scores were characterized by the activation of stromal pathways and immunosuppression.ConclusionThis study revealed the potential effects of CRGs on the TME, clinicopathological features, and prognosis of TNBC. The CRGs were closely associated with the tumor immunity of TNBC and are a potential tool for predicting patient prognosis. Our data provide new directions for the development of novel drugs in the future.

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Regulatory T cells: Their role in triple‐negative breast cancer progression and metastasis

Cited by 26 publications

References 86 publications

3D Collagen Fiber Concentration Regulates Treg Cell Infiltration in Triple Negative Breast Cancer

3D Collagen Fiber Concentration Regulates Treg Cell Infiltration in Triple Negative Breast Cancer

COL11A1 serves as a biomarker for poor prognosis and correlates with immune infiltration in breast cancer

Prognostic analysis of cuproptosis-related gene in triple-negative breast cancer

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