scholarly journals Rates of immune cell infiltration in patients with triple-negative breast cancer by molecular subtype

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0204513 ◽  
Author(s):  
Kenichi Harano ◽  
Ying Wang ◽  
Bora Lim ◽  
Robert S. Seitz ◽  
Stephan W. Morris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Molecular Subtype ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Classification of triple-negative breast cancer based on immune cell infiltration

2020 ◽  
Author(s):  
Wenji Shi ◽  
Dan Wang ◽  
Luz Angela Torres-de la Roche ◽  
Rui Zhuo ◽  
Rudy Leon De Wilde
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
B Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Immune Phenotype ◽  
Cluster A

Abstract Background Although the classification system of triple-negative breast cancer(TNBC) has become more and more perfect, there is no report on the immune subtype of triple-negative breast cancer based on immune cell infiltration. Results According to immune infiltrating cells, data from 360 patients were divided into cluster A (subtype 1 and subtype 3) and cluster B (subtype 2; with poorly immune phenotype). Expression of memory B cells, naïve B cells, M0 macrophages, M1 macrophages, CD4 memory activated T cells, and CD4 naïve T cells were significantly higher in cluster A (P < 0.05). In contrast, the expression of M2 macrophages and resting mast cells were higher in cluster B (P < 0.05). GSVA results show that B cell receptor pathway and JAK-STAT pathway are activated and more frequently altered in cluster A (P < 0.05). mTOR pathway alterations usually appear in cluster B (P < 0.05). Compared with cluster A, the risk of recurrence in cluster B patients is significantly increased (P < 0.05). Conclusions This analysis of tumor microenvironment revealed the multifaceted nature of TNBC and its impact on patient prognosis, being recurrence more often in those with poorly immune phenotype. These results provide a reference for further exploration of the heterogeneity of TNBC.

scholarly journals Association of Galectin 9 Expression with Immune Cell Infiltration, Programmed Cell Death Ligand-1 Expression, and Patient’s Clinical Outcome in Triple-Negative Breast Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1383
Author(s):  
Mi-Ha Ju ◽  
Kyung-Do Byun ◽  
Eun-Hwa Park ◽  
Jin-Hwa Lee ◽  
Song-Hee Han
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Clinical Outcome ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

Galectin-9 (Gal-9) is an immune checkpoint protein that facilitates T cell exhaustion and modulates the tumor-associated microenvironment, and could be a potential target for immune checkpoint inhibition. This study was conducted to assess Gal-9 expression in triple-negative breast cancer (TNBC) and evaluate its association with programmed cell death ligand 1 (PD-L1) expression and immune cell infiltration in tumors and the clinical outcome of patients. Overall, 109 patients with TNBC were included. Gal-9 expression was assessed its relationships with tumor clinicopathologic characteristics, tumor-infiltrating lymphocyte (TIL) levels, PD-L1+ immune cells, and tumor cells by tissue microarray and immunohistochemistry. Low Gal-9 expression was statistically correlated with higher tumor stage (p = 0.031) and presence of lymphovascular invasion (p = 0.008). High Gal-9 expression was associated with a high level of stromal TILs (sTIL; p = 0.011) and positive PD-L1 expression on tumor cells (p = 0.004). In survival analyses, low Gal-9 expression was associated with significantly poor OS (p = 0.013) in patients with TNBC with PD-L1 negativity in tumor cells. Our findings suggest that increased Gal-9 expression is associated with changes in the antitumor microenvironment, such as increased immune cell infiltration and antimetastatic changes. This study emphasizes the predictive value and promising clinical applications of Gal-9 in TNBC.

scholarly journals Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Chundi Gao ◽  
Huayao Li ◽  
Cun Liu ◽  
Xiaowei Xu ◽  
Jing Zhuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mutation Rate ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Cancer Genome ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Tumor Mutation Burden ◽  
Mutation Burden

In recent years, the emergence of immunotherapy has provided a new perspective for the treatment and management of triple-negative breast cancer (TNBC). However, the relationship between tumor mutation burden (TMB) and immune infiltration and the prognosis of TNBC remains unclear. In this study, to explore the immunogenicity of TNBC, we divided patients with TNBC into high and low TMB groups based on the somatic mutation data of TNBC in The Cancer Genome Atlas (TCGA), and screened out genes with mutation rate ≥10. Then, Kaplan-Meier survival analysis revealed that the 5-year survival rate of the high TMB group was much higher than that of the low TMB group and the two groups also showed differences in immune cell infiltration. Further exploration found that the FAT3 gene, which displays significant difference and a higher mutation rate between the two groups, is not only significantly related to the prognosis of TNBC patients but also exhibits difference in immune cell infiltration between the wild group and the mutant group of the FAT3 gene. The results of gene set enrichment analysis and drug sensitivity analysis further support the importance of the FAT3 gene in TNBC. This study reveals the characteristics of TMB and immune cell infiltration in triple-negative breast cancer and their relationship with prognosis, to provide new biomarkers and potential treatment options for the future treatment of TNBC. The FAT3 gene, as a risk predictor gene of TNBC, is considered a potential biological target and may provide new insight for the treatment of TNBC.

scholarly journals Inflammation Is Associated with Worse Outcome in the Whole Cohort but with Better Outcome in Triple-Negative Subtype of Breast Cancer Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Masanori Oshi ◽  
Stephanie Newman ◽  
Yoshihisa Tokumaru ◽  
Li Yan ◽  
Ryusei Matsuyama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
Neoadjuvant Treatment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Inflammatory Pathway ◽  
Gene Set ◽  
Breast Cancer Cohort ◽  
Ifn Γ

Inflammation has been linked with cancer, but whether it is part of the problem or part of the solution remains to be a matter of debate in breast cancer. Our group and others have demonstrated that inflammation aggravates cancer progression; however, some claim that inflammation may support immune cell infiltration and suppress cancer. We defined the gene set variation analysis of the Molecular Signatures Database Hallmark inflammatory response gene set as the inflammatory pathway score and analyzed 3632 tumors in total from 4 breast cancer cohorts (METABRIC, TCGA, GSE25066, and GSE21094). In the whole breast cancer cohort, high-score tumors were associated with aggressive clinical characteristics, such as worse disease specific survival, higher Nottingham histological grade, and younger age. Inflammatory score was significantly higher in triple-negative (TNBC) as well as basal and normal subtypes compared with the other subtypes, which suggest that the detrimental effect of high level of inflammation may be because it includes a more aggressive subtype. On the contrary, high score within TNBC was significantly associated with better survival. TNBC with high score enriched not only IFN-α, IFN-γ response, IL-2/STAT5 signaling, Allograft rejection, Complement, p53 pathway, Reactive Oxygen, and Apoptosis but also TNF-α signaling, IL6-JAK-STAT signaling, TGF-β signaling, Coagulation, Angiogenesis, EMT, KRAS signaling, and PI3K-AKT-MTOR signaling gene sets. High score was associated with mainly favorable anticancerous immune cell infiltration as well as Leukocyte fraction, TIL regional fraction, Lymphocyte infiltration, IFN-γ response, TGF-β response, and cytolytic activity scores. Although the inflammatory pathway score was not associated with neoadjuvant treatment response, it associated with expressions of immune checkpoint molecules. In conclusion, inflammation was associated with worse outcome in the whole breast cancer cohort, but with better outcome in TNBC, which was associated with favorable anticancerous immune response and immune cell infiltrations.

scholarly journals Triple-Negative Breast Cancer with High Levels of Annexin A1 Expression Is Associated with Mast Cell Infiltration, Inflammation, and Angiogenesis

2019 ◽  
Vol 20 (17) ◽  
pp. 4197 ◽  
Author(s):  
Maiko Okano ◽  
Masanori Oshi ◽  
Ali Linsk Butash ◽  
Eriko Katsuta ◽  
Kazunoshin Tachibana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mast Cell ◽  
Mast Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Cell ◽  
High Expression ◽  
Cell Infiltration ◽  
Annexin A1 ◽  
Aggressive Phenotype

Annexin A1 (ANXA1) is a phospholipid-linked protein involved in inflammation, immune response, and mast cell reactivity. Recently, we reported that ANXA1 is associated with aggressive features of triple-negative breast cancer (TNBC); however, its clinical relevance remains controversial. We hypothesized that human TNBC with high expression of ANXA1 mRNA is associated with pro-cancerous immune cell infiltration, including mast cells, and with an aggressive phenotype. Clinical and RNA-seq data were obtained from The Cancer Genome Atlas (TCGA, n = 1079) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1904). TNBC patients had significantly higher levels of ANXA1 expression compared to the other subtypes in both TCGA and METABRIC cohorts (p < 0.001). ANXA1 protein expression was assessed by immunohistochemistry in Japanese TNBC patient cohort (n = 48), where 17 cases (35.4%) had positive ANXA1 staining, and their overall survival was significantly shorter compared with negative staining group (p = 0.008). The CIBERSORT algorithm was used to calculate immune cell infiltrations. ANXA1 high tumors were associated with activated mast cells and M2 macrophages (p > 0.01), but did not show any association with tumor heterogeneity nor cytolytic activity. High expression of ANXA1 group enriched inflammation, epithelial-to-mesenchymal transition (EMT), and angiogenesis-related genes in a gene set enrichment assay in both cohorts. To our knowledge, this is the first study to demonstrate that ANXA1 is associated with infiltration of mast cells and inflammation that is associated with the aggressive phenotype of TNBC, such as EMT and angiogenesis.

scholarly journals Pilose antler polypeptides promote chemosensitization and T-cell infiltration of triple-negative breast cancer

2021 ◽  
Vol 85 ◽  
pp. 104664
Author(s):  
Mohan Li ◽  
Kexin Zheng ◽  
Shiliang Ma ◽  
Pengpeng Hu ◽  
Bo Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Infiltration ◽  
T Cell Infiltration

scholarly journals Expression of Phosphorylated BRD4 Is Markedly Associated with the Activation Status of the PP2A Pathway and Shows a Strong Prognostic Value in Triple Negative Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1246
Author(s):  
Marta Sanz-Álvarez ◽  
Ion Cristóbal ◽  
Melani Luque ◽  
Andrea Santos ◽  
Sandra Zazo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Molecular Target ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Bet Inhibitors ◽  
Brd4 Inhibition ◽  
Bet Protein

The bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, has emerged in the last years as a promising molecular target in many tumors including breast cancer. The triple negative breast cancer (TNBC) represents the molecular subtype with the worst prognosis and a current therapeutic challenge, and TNBC cells have been reported to show a preferential sensitivity to BET inhibitors. Interestingly, BRD4 phosphorylation (pBRD4) was found as an alteration that confers resistance to BET inhibition and PP2A proposed as the phosphatase responsible to regulate pBRD4 levels. However, the potential clinical significance of pBRD4, as well as its potential correlation with the PP2A pathway in TNBC, remains to be investigated. Here, we evaluated the expression levels of pBRD4 in a series of 132 TNBC patients. We found high pBRD4 levels in 34.1% of cases (45/132), and this alteration was found to be associated with the development of patient recurrences (p = 0.007). Interestingly, BRD4 hyperphosphorylation predicted significantly shorter overall (p < 0.001) and event-free survival (p < 0.001). Moreover, multivariate analyses were performed to confirm its independent prognostic impact in our cohort. In conclusion, our findings show that BRD4 hyperphosphorylation is an alteration associated with PP2A inhibition that defines a subgroup of TNBC patients with unfavorable prognosis, suggesting the potential clinical and therapeutic usefulness of the PP2A/BRD4 axis as a novel molecular target to overcome resistance to treatments based on BRD4 inhibition.

Sign in / Sign up

Export Citation Format

Share Document