Lymphoid environment in molecular subtypes of breast cancer

Glajcar, Anna; Szpor, Joanna; Tyrak, Katarzyna Ewa; Streb, Joanna; Hodorowicz-Zaniewska, Diana; Okoń, Krzysztof

doi:10.5114/pjp.2018.76700

Cited by 3 publications

(5 citation statements)

References 53 publications

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“…Tumor immune infiltration was an independent prognostic factor for survival and was associated with the prognosis of malignant tumor ( Loi et al, 2013 ; Glajcar et al, 2018 ), demonstrating that tumor immune infiltration may serve as a promising target for immune-based therapy and cancer prevention ( Thompson et al, 2016 ). Therefore, we investigated whether the expression levels of TMPRSS2 in different types of cancers were correlated with immune infiltration levels.…”

Section: Resultsmentioning

confidence: 99%

TMPRSS2 Serves as a Prognostic Biomarker and Correlated With Immune Infiltrates in Breast Invasive Cancer and Lung Adenocarcinoma

Xiao

Shan

Niu

et al. 2022

Front. Mol. Biosci.

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TMPRSS2 is a transmembrane serine protease and plays a pivotal role in coronavirus disease 2019 (COVID-19). However, the correlation of TMPRSS2 with prognosis and immune infiltration in tumors has not yet been explored. Here, we analyzed the expression of TMPRSS2 in Oncomine and TIMER databases, the correlation between TMPRSS2 and overall survival in the PrognoScan, Kaplan-Meier plotter, and GEPIA databases. The association between TMPRSS2 and immune infiltration levels was investigated in the TIMER database. In addition, the prognosis of TMPRSS2 related to immune cells in cancers was analyzed. Quantitative real-time PCR (qRT-PCR) confirmed that TMPRSS2 was upregulated in lung adenocarcinoma (LUAD) and downregulated in breast invasive carcinoma (BRCA). We demonstrated that high TMPRSS2 expression was associated with favorable prognosis in LUAD, but it was associated with poor prognosis in BRCA. Interestingly, we found that TMPRSS2 expression was significantly correlated with immune infiltration of B cells, CD4+ T cells, macrophages, and dendritic cells in LUAD, and it was positively correlated with the infiltrating levels of CD8+ T cells, CD4+ T cells, neutrophils, and dendric cells in BRCA. Consistent with the prognosis of TMPRSS2 in LUAD and BRCA, the high expression level of TMPRSS2 has a favorable prognosis in enriched immune cells such as B cells, macrophages, and CD4+ T cells in LUAD, and it has a poor prognosis in CD4+ T cells and CD8+ T cells in BRCA. In conclusion, our results indicate that the prognosis of TMPRSS2 in LUAD and BRCA is significantly correlated with immune cells infiltration. Our study comprehensively revealed the relationship between the prognosis of TMPRSS2 in pan-cancers and tumor immunity.

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Section: Resultsmentioning

confidence: 99%

TMPRSS2 Serves as a Prognostic Biomarker and Correlated With Immune Infiltrates in Breast Invasive Cancer and Lung Adenocarcinoma

Xiao

Shan

Niu

et al. 2022

Front. Mol. Biosci.

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“…Our recent research studies aimed at evaluation of tumor microenvironment in primary invasive breast cancer have shown associations between higher quantities of mast cells and beneficial prognostic indicators [40] and relationships between T cell, B cell, and NK cell infiltrates and adverse clinical factors [41]. These findings induced us to presently investigate infiltrates of several T cell subpopulations in this disease.…”

Section: Discussionmentioning

confidence: 99%

The composition of T cell infiltrates varies in primary invasive breast cancer of different molecular subtypes as well as according to tumor size and nodal status

et al. 2019

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T lymphocytes are the most numerous immune cells in tumor-associated infiltrates and include several subpopulations of either anticancer or pro-tumorigenic functions. However, the associations between levels of different T cell subsets and breast cancer molecular subtypes as well as other prognostic factors have not been fully established yet. We performed immunohistochemistry for CD8 (cytotoxic T cells (CTL)), FOXP3 (regulatory T cells (Tregs)), and GATA3 (Th2 cells) in 106 formalin-fixed paraffin-embedded invasive breast cancer tissue samples and analyzed both the numbers and percentages of investigated cells in tumor-associated infiltrates. We observed that triple-negative breast cancer (TNBC) and HER2+ non-luminal breast tumors were associated with more numerous CTLs and Tregs and a higher Treg/Th2 cell ratio as compared with luminal A subtype. A higher Treg percentage was related to a decreased hormone receptor expression, an increase in the Ki67 level, a greater tumor size of luminal tumors, and the presence of lymph node metastases. Moreover, differences in the composition of T cell infiltrates were associated with HER2 status and histologic grade and type, and a distinct immune pattern was observed in tumors of different phenotypes regarding pT stage and nodal status. The results of our work show the diversity of T cell infiltrates in primary invasive breast cancers of different phenotypes and suggest that progression of luminal or non-luminal tumors is related to distinct tumor-associated T cell composition.

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“…Due to significantly lower rates of immunological markers and modest immune infiltrate as compared to other subtypes, luminal A BC is considered to be non-immunogenic [ 5 , 9 , 21 , 23 , 24 ]. Thus, the vast majority of research investigating immune microenvironment in BC focus on its non-luminal types.…”

Section: Discussionmentioning

confidence: 99%

“…In clinical practice, the most commonly used molecular classification of BC is St Gallen 2015 International Expert Consensus, based on the expression of an estrogen receptor (ER), progesterone receptor (PR), a receptor for human epidermal growth factor 2 (HER2) in cancer cells and Ki67 protein, which reflects proliferation levels [ 4 , 5 ]. Currently, five molecular types of BC are distinguished: luminal type A (ER + , PR + , HER2-, low Ki67), HER2- luminal type B (ER + , low PR or high Ki67, HER2-), luminal B/HER2 + (ER + and HER2 +), HER2-positive non-luminal (ER-, PR-, HER2 +).…”

Section: Introductionmentioning

confidence: 99%

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Nodal status in luminal A invasive breast cancer: relationships with cytotoxic CD8 + and regulatory FOXP3 + cells tumor-associated infiltrate and other prognostic factors

et al. 2021

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Luminal A breast cancers are generally associated with low metastatic potential and good prognosis. However, there is a proportion of patients, who present with metastases in lymph nodes. The aim of our study was to determine the association between the number of positive lymph nodes and infiltrates of tumor-associated cytotoxic CD8 + (CTLs), regulatory FOXP3 + T cells (Tregs), as well as other prognostic factors. Immunohistochemistry (IHC) for CD8 + and FOXP3 + was performed in 87 formalin-fixed paraffin-embedded primary breast cancer tissues, and cell infiltrate was assessed under light microscope. We observed that node-positive cases were associated with higher numbers of Treg cells and lower CTL/Treg ratio. There was also an inverse correlation between the CTL/Treg ratio and the number of metastatic lymph nodes. Similar relationships were found between the number of metastatic lymph nodes and Treg density or CTL/Treg ratio in pT1 BC. An elevated intratumoral CTL/Treg ratio was associated with pN0 stage. The relationship between lymphovascular invasion (LVI) and Treg density was also noted in node-negative tumors. In addition, more advanced nodal stage was related to LVI, higher pT, and lower PR expression. The numbers of CD8 + and FOXP3 + were also associated with tumor size, histologic grade, PR expression, and mitotic index. The results of our study suggested that the levels of tumor-infiltrating regulatory and cytotoxic cells as well as the balance between them play a role in lymphovascular spread of luminal A breast cancers.

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Lymphoid environment in molecular subtypes of breast cancer

Cited by 3 publications

References 53 publications

TMPRSS2 Serves as a Prognostic Biomarker and Correlated With Immune Infiltrates in Breast Invasive Cancer and Lung Adenocarcinoma

TMPRSS2 Serves as a Prognostic Biomarker and Correlated With Immune Infiltrates in Breast Invasive Cancer and Lung Adenocarcinoma

The composition of T cell infiltrates varies in primary invasive breast cancer of different molecular subtypes as well as according to tumor size and nodal status

Nodal status in luminal A invasive breast cancer: relationships with cytotoxic CD8 + and regulatory FOXP3 + cells tumor-associated infiltrate and other prognostic factors

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