Triple‐negative breast cancer—Role of immunology: A systemic review

Öner, Gizem; Altıntaş, Sevilay; Cantürk, Zafer; Tjalma, Wiebren A.A.; Verhoeven, Yannick; Berckelaer, Christophe Van; Berneman, Zwi; Peeters, Marc; Pauwels, Patrick; Dam, Peter van

doi:10.1111/tbj.13696

Cited by 42 publications

(40 citation statements)

References 23 publications

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“…To examine whether MATR3 expression is correlated with the aggressiveness and poor prognosis of breast cancer, we compared its expression between triple-negative breast cancer (TNBC) and BLBC and other breast cancer subtypes. TNBC and BLBC represent ~ 15-20% of all breast cancer cases and are generally considered highly aggressive and metastatic [24,25]. RNA-sequencing dataset analysis [26,27] demonstrated that MATR3 expression was significantly lower in the TNBC & BLBC compared to the other subtypes ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Tumor suppressive function of Matrin 3 in the basal-like breast cancer

et al. 2020

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Background Basal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is an aggressive and highly metastatic subtype of human breast cancer. The present study aimed to elucidate the potential tumor-suppressive function of MATR3, an abundant nuclear protein, in BLBC/TNBC, whose cancer-relevance has not been characterized. Methods We analyzed in vitro tumorigenecity by cell proliferation and soft agar colony formation assays, apoptotic cell death by flow cytometry and Poly (ADP-ribose) polymerase (PARP) cleavage, epithelial-mesenchymal transition (EMT) by checking specific EMT markers with real-time quantitative PCR and in vitro migration and invasion by Boyden Chamber assays. To elucidate the underlying mechanism by which MATR3 functions as a tumor suppressor, we performed Tandem affinity purification followed by mass spectrometry (TAP-MS) and pathway analysis. We also scrutinized MATR3 expression levels in the different subtypes of human breast cancer and the correlation between MATR3 expression and patient survival by bioinformatic analyses of publicly available transcriptome datasets. Results MATR3 suppressed in vitro tumorigenecity, promoted apoptotic cell death and inhibited EMT, migration, and invasion in BLBC/TNBC cells. Various proteins regulating apoptosis were identified as MATR3-binding proteins, and YAP/TAZ pathway was suppressed by MATR3. MATR3 expression was inversely correlated with the aggressive and metastatic nature of breast cancer. Moreover, high expression levels of MATR3 were associated with a good prognosis of breast cancer patients. Conclusions Our data demonstrate that MATR3 functions as a putative tumor suppressor in BLBC/TNBC cells. Also, MATR3 potentially plays a role as a biomarker in predicting chemotherapy-sensitivity and patient survival in breast cancer patients.

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Section: Resultsmentioning

confidence: 99%

Tumor suppressive function of Matrin 3 in the basal-like breast cancer

et al. 2020

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“…TIL levels are higher in highly proliferating tumors, including human epidermal growth factor receptor 2 (HER2)-positive and TNBC (3). TILs have a strong prognostic and predictive significance, and high TIL levels are positively correlated with pathological complete response rate and patient survival rate (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Meng

Huang

et al. 2020

Front. Oncol.

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Objectives: Tumor-infiltrating lymphocytes (TILs) have been identified as a significant prognostic indicator of response to neoadjuvant therapy and immunotherapy for triple-negative breast cancer (TNBC) patients. Herein, we aim to assess the association between TIL levels and mammographic features in TNBC patients. Methods: Forty-three patients with surgically proven TNBC who underwent preoperative mammography from January 2018 to December 2018 were recruited. Pyradiomics software was used to extract 204 quantitative radiomics features, including morphologic, grayscale, and textural features, from the segmented lesion areas. The correlation between radiological characteristics and TIL levels was evaluated by screening the most statistically significant radiological features using Mann-Whitney U-test and Pearson correlation coefficient. The patients were divided into two groups based on tumor TIL levels: patients with TIL levels <50% and those with TIL levels ≥50%. The correlation between TIL levels and clinicopathological characteristics was assessed using the chi-square test or Fisher's exact test. Mann-Whitney U-test and Pearson correlation coefficient were used to analyze the statistical significance and Pearson correlation coefficient of clinical pathological features, age, and radiological features. Conclusion: Mammography features not only distinguish high and low TIL levels in TNBC patients but also can act as imaging biomarkers to enhance diagnosis and the response of patients to neoadjuvant therapies and immunotherapies.

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“…Breast cancer is a prevalent malignancy in female globally, with ~ 1.4 million new cases diagnosed annually [ 1 ], of which triple‐negative breast cancer (TNBC) represents approximately 15–20% and have the highest genomic instability rates when compared with other breast cancer subtypes [ 2 ]. Previous studies have shown that TNBC can stimulate the immune system to form a tumor microenvironment (TME) where immune cells are the main component which can be identified as potential prognostic factors for TNBC patients [ 3 ]. Tumor-infiltrating lymphocytes (TILs) play an important role in promoting host protection against cancer and facilitating tumor escape from immune destruction [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive genomic and immunophenotypic analysis of CD4 T cell infiltrating human triple-negative breast cancer

Zhang

Qin

et al. 2020

Cancer Immunol Immunother

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The aim of this study is to investigate the gene expression module of tumor-infiltrating CD4+T cells and its potential roles in modulating immune cell functions in triple-negative breast cancer. Differentially expressed genes were identified by comparison of the expression profile in CD4+T cells isolated from tumor tissues and peripheral blood of TNBC patients respectively. The differential expression analysis was conducted using R, and then the functional and pathway enrichment of the DEGs were analyzed using GSEA, followed by integrated regulatory network construction and genetic analysis of tumor-infiltrating immune cells based on a scientific deconvolution algorithm. As a result, abundant Treg and exhausted lymphocytes were detected, accompanied by largely decreased of effector/memory and cytotoxic T cells. Immune-related gene correlation analysis showed that the extent of follicular helper T cells gene expression signatures were inversely associated with those of CD4+ naive T cells and CD4+ memory resting T cells, but positively correlated with that of CD4+ memory activated T cells. In addition, we found five core genes including IFNG, CTLA4, FAS, CXCR6, and JUN were significantly over expressed in CD4+ TILs which may contribute to exhaustion of lymphocytes and participate in biological processes associated with regulation of chemotaxis. Study provides a comprehensive understanding of the roles of DEGs associated with the chemotactic and exhausted immunophenotypes of CD4+ TILs that are a valuable resource from which future investigation may be carried out to better understand the mechanisms that promote TNBC progression.

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Triple‐negative breast cancer—Role of immunology: A systemic review

Abstract: Breast J. 2020;26:995-999. wileyonlinelibrary.com/journal/tbj | 995

Cited by 42 publications

References 23 publications

Tumor suppressive function of Matrin 3 in the basal-like breast cancer

Tumor suppressive function of Matrin 3 in the basal-like breast cancer

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Comprehensive genomic and immunophenotypic analysis of CD4 T cell infiltrating human triple-negative breast cancer

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