Distribution and prognostic value of tumor‑infiltrating T cells in breast cancer

Meng, Shaoda; Li, Li; Zhou, Meiling; Jiang, Wan-jie; Niu, Heng; Yang, Kunxian

doi:10.3892/mmr.2018.9460

Cited by 19 publications

(29 citation statements)

References 34 publications

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“…Clinically, an increased frequency of Tregs is associated with BC progression, histological grade, estrogen receptor negativity, HER-2 positivity, and molecular subtype in BC [55]. HER-2 positive BC and TNBC subtypes have significantly higher amounts of Treg cells, and decreased levels of CD8+T cells compared with the luminal subtype [55]. The extent of Treg cells also predicts worse outcome in TNBC patients [56].…”

Section: Hcmv M2 and T Regulatory Cellsmentioning

confidence: 99%

A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity

Geisler

Touma

Rahbar

et al. 2019

Cancers

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Previously recognized classical human onco-viruses can regulate complex neoplastic events, and are estimated to play a role during carcinogenesis in 15–20% of cancer cases. Although the DNA and gene products of several viruses have been found in breast tumors, none of the classical onco-viruses have definitely been linked to the initiation of breast cancer. However, recent evidence shows that human cytomegalovirus (HCMV) gene products are found in >90% of tumors and metastases of breast cancers, and their increased expression can be correlated to a more aggressive breast cancer phenotype. Supporting the active role of HCMV in breast cancer, a specific HCMV strain, HCMV-DB, was recently shown to exert oncogenic transformational activity in breast epithelial cells in vitro, and to give rise to fast-growing, triple-negative breast tumors when injected into immune deficient mice. The same observation holds true for clinical studies implying increased HCMV protein expression in triple negative breast cancer biopsies. In addition to functionally being able to hijack tumor-promoting cellular events, HCMV is known to exhibit a wide range of immunosuppressive effects, which can have radical impact on the tumor microenvironment. HCMV infected cells can avoid recognition and elimination by the immune system by orchestrating polarization of immunosuppressive type II macrophages, preventing antigen presentation, by expressing T cell inhibitory molecules, and possibly, by the induction of regulatory T (Treg) cell responses. These actions would be especially deleterious for the antigenic activation and proliferation of tumor specific CD8+ cytotoxic T lymphocytes (CTLs), whose effector functions have recently been targeted by successful, experimental immunotherapy protocols. The recognition of alternative causes and drivers of breast cancer is a pivotal research topic for the development of diagnostics and novel, effective preventive and therapeutic strategies targeting both tumor cells and their microenvironments.

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Section: Hcmv M2 and T Regulatory Cellsmentioning

confidence: 99%

A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity

Geisler

Touma

Rahbar

et al. 2019

Cancers

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“…Immune cells, including dendritic cells and CD8 + cytotoxic T lymphocytes, could function as promising targets for the therapy of bone metastasis [32]. In breast cancer, CD8 + T cells and regulatory T cells were suggested as the reliable prognostic biomarker [33]. CTLA4 and PD-1 had been suggested as immune checkpoint for cancer immunotherapy [34].…”

Section: Discussionmentioning

confidence: 99%

Identification of therapeutic targets and prognostic biomarkers among STAT family in glioblastoma

Li¹,

Zhou²,

Deng³

et al. 2020

Preprint

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Background: Glioblastoma (GBM) is the most common and aggressive primary brain malignancies with high incidence and mortality. The aberrant activation of STAT signaling was confirmed to result in tumor pathogenesis and progress by regulating cell cycle, cell survival, and immune response. Methods: The clinical significance of and regulation network of STAT family in GBM were explored with several web applications or database. Results: The level of STAT1/3/5A/5B/6 were increased in GBM while STAT4 level was decreased. GBM patients with high expression of STAT1/2/3/5A/6 and low expression of STAT4/5B had a worse overall survival. Among the STAT family, STAT 4 and STAT6 were the top two frequently mutated genes. Correlation suggested a low to moderate correlation among STAT family. STAT family were also involved in the activation or inhibition of the famous cancer related pathways. Immune infiltrates analysis suggested that STAT5A level showed significantly correlated with the abundance of immune cells and the level of immune gene biomarkers. GO functions and KEGG pathways analysis revealed that STAT5A was involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, and TNF signaling pathway. Moreover, we also identified several Kinase and transcription factor targets of STAT5A in GBM. Conclusions: Our results revealed the therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM, laying the foundation for further studies about STAT family in therapy and prognosis of GBM.

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“…A positive correlation was observed in multiple studies between the number of tumor infiltrating cytotoxic CD8+ T cells and clinical outcome in BC that may improve patient survival [13,26,36,41].…”

Section: Cd8+ T Lymphocytes and Cd4+ T Helper Cells May Promote Tumormentioning

confidence: 93%

“…In addition, we analyzed the frequency of CD4+ Tregs among clinically defined surrogates of BC molecular subtypes including ER+, Her2+, and triple negative BC in order to explore whether any particular clinical disease correlates were associated with increased number of CD4+ Tregs. Increased CD4+ Tregs frequency was associated with poor prognostic characteristics such as higher histological grade, lymph node metastasis [14,35,36].…”

Section: Cd8+ T Lymphocytes and Cd4+ T Helper Cells May Promote Tumormentioning

confidence: 99%

Association of CD4+ CD25+ FOXP3+ regulatory T-cells and human papilloma virus infection in Egyptian Women with breast cancer

Tawfeik

Mora

Osman

et al. 2020

Preprint

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Several subsets of regulatory CD4+ T cells (CD4+ Tregs) have been described in peripheral blood and tumor microenvironment and blood of breast cancer (BC) patients and may play a key role in the progression of BC. High-risk human papilloma virus (HPV) have a causal role in a significant proportion of cervical, and head, and neck tumors and may play an important role in evoking neoplasia in BC. In this study we assessed the prevalence of CD4+Tregs (CD4+CD25+ FOXP3+ cells) and CD3+ CD8+ T cells by flow cytometry in peripheral blood from a total of 55 Egyptian women, including 20 treatment-naïve BC, 15 with breast benign lesions (BBL) and 20 healthy volunteers (HV). High-risk HPV genotype type 16, 18, and 31 was investigated in breast tissue from all BC and BBL patients using Real-Time PCR. HPV was detected in 4 BC, but in none of BBL patients. The frequency of CD4+ Tregs was significantly higher in BC compared to BBL and HV, (p < 0.001). In addition, we observed a significantly higher frequency of CD3+ CD8+ T cells in peripheral blood of patients with late stage III compared to early stage I and II BC (p = 0.011). However, there was no significant association between the ratio of CD8+ T cell to CD4+ Tregs frequencies and the expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). In conclusion, CD4+ Tregs may contribute to progression BC in Egyptian women with HPV infection. The potential role CD4+ Tregs as a prognostic or predictive parameter should be analyzed in a larger longitudinal study with sufficient follow-up time.

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Distribution and prognostic value of tumor‑infiltrating T cells in breast cancer

Cited by 19 publications

References 34 publications

A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity

A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity

Identification of therapeutic targets and prognostic biomarkers among STAT family in glioblastoma

Association of CD4+ CD25+ FOXP3+ regulatory T-cells and human papilloma virus infection in Egyptian Women with breast cancer

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