Identification of CTLA-4 associated with tumor microenvironment and competing interactions in triple negative breast cancer by co-expression network analysis

Peng, Ziqi; Su, Peng; Yang, Yuhong; Yao, Xue Qing; Zhang, Yiqi; Jin, Feng; Yang, Bowen

doi:10.7150/jca.46301

Cited by 36 publications

(22 citation statements)

References 37 publications

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“…Such changes were not found when MCF-7 cells (ER-positive) were used, thus suggesting the need for careful consideration of immunotherapy application in breast cancers. In the study of Peng et al, the molecular analysis of CTLA-4 expression on different subtypes of breast cancer cells showed the highest CTLA-4 level in TNBC, which seems to be a direct confirmation of our results [33].…”

Section: Discussionsupporting

confidence: 90%

Differential Response of MDA-MB-231 and MCF-7 Breast Cancer Cells to In Vitro Inhibition with CTLA-4 and PD-1 through Cancer-Immune Cells Modified Interactions

Grubczak

Krętowska-Grunwald

Groth

et al. 2021

Cells

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Drugs targeting immune checkpoint molecules have been found effective in melanoma, lung cancer, and other malignancies treatment. Recent studies on breast cancer demonstrated the significance of inhibitory anti-CTLA-4 and anti-PD-1 in the regulation of disease progression. However, seemingly the same types of breast cancer do not always respond unambiguously to immunotherapy. Thus, here we set out to analyze the in vitro effects of inhibiting CTLA-4 and PD-1 on interactions between co-cultured lymphocytes and two selected breast adenocarcinoma cell lines. Breast cancer cells were co-cultured with lymphocytes to evaluate the effects of CTLA-4 and PD-1 inhibition. Proliferation, cell cycle, and viability assessment were measured in cancer cells. IFN-gamma, IL-10, perforin, granzyme B production, and CTLA-4 and PD-1 expression were analyzed in lymphocytes. We found that administration of anti-CTLA-4 improved the anti-cancer activity of T cells with reduced proliferation and viability of MDA-MB-231. Lack of response was observed in the context of MCF-7. In addition, differential expression of checkpoint proteins was found between studied cancer cells lines. Inhibition of molecules was followed by IL-10 and IFN-gamma decrease in lymphocytes co-cultured with MDA-MB-231, not demonstrated in reference to MCF-7. Furthermore, CTLA-4 blockage was associated with reduction of CTLA-4+ and PD-1+ lymphocytes in MDA-MB-231, with a significant increase in MCF-7, reduced by anti-PD-1. Altogether, our study revealed that anti-CTLA-4 and anti-PD-1 treatment can improve lymphocytes effects on breast cancer cells. Favorable effects seemed to be related to breast cancer cells features as differential responses were reported. Novel blocking antibodies strategies should be tested for more effective cancer inhibition.

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Section: Discussionsupporting

confidence: 90%

Differential Response of MDA-MB-231 and MCF-7 Breast Cancer Cells to In Vitro Inhibition with CTLA-4 and PD-1 through Cancer-Immune Cells Modified Interactions

Grubczak

Krętowska-Grunwald

Groth

et al. 2021

Cells

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“…showing a significant effect in the treatment of TNBC. 148,150,153,154,165,166 Discussion TNBC is the most aggressive and metastatic subtype of breast cancer with high intrinsic heterogeneity. The lack of estrogen receptor (ER), progesterone receptor (PR), and HER-2 expression means that there are few targeted drugs available to patients with TNBC.…”

Section: Tnbc With Immune Checkpointmentioning

confidence: 99%

“…The combination of two different classes of antibody drugs overcame the immunosuppressive effect of tumor tissues and transformed the immunosuppressive condition of the tumor microenvironment into a matrix environment with anticancer function, showing a significant effect in the treatment of TNBC. 148 , 150 , 153 , 154 , 165 , 166 …”

Section: Tnbc With Immune Checkpointmentioning

confidence: 99%

The Characteristics of Tumor Microenvironment in Triple Negative Breast Cancer

Fan¹,

He²

2022

CMAR

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Triple-negative breast cancer (TNBC) is a special subtype of breast cancer, accounting for 10-20% of breast cancers with high intrinsic heterogeneity. Its unique immune microenvironment, including high expression of vascular endothelial growth factors, tumor infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and other molecules that promote the growth and migration of tumor cells, has been shown to play a dual role in the occurrence, growth, and metastasis of TNBC. Understanding the TNBC microenvironment is of great significance for the prognosis and treatment of TNBC. In this article, we describe the composition and function of immune cells in the TNBC microenvironment and summarize the major cytokine growth factors and chemokines in the TNBC microenvironment. Finally, we discuss the progress of TNBC, cytokine-induced killer cell therapy, and immune checkpoint therapy.

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“…The high expression of CTLA-4 in breast cancer cells is associated with poor prognosis ( 84 , 85 ). Among all types of breast cancer, the expression of CTLA-4 is highest in TNBC ( 86 ). Inhibition of CTLA-4 is able to prevent T-cell suppression and enhance the anti-tumor activity of T cells, which is a potential immune-related target for treating TNBC.…”

Section: Immune Checkpoint Inhibitionmentioning

confidence: 99%

Research progress on immunotherapy in triple‑negative breast cancer (Review)

Zhang

Jiang

et al. 2022

Int J Oncol

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Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive malignancy. Due to the absence of estrogen receptors and progesterone receptors and the lack of overexpression of human epidermal growth factor receptor 2, TNBC responds poorly to endocrine and targeted therapies. As a neoadjuvant therapy, chemotherapy is usually the only option for TNBC; however, chemotherapy may induce tumor resistance. The emergence of immunotherapy as an adjuvant therapy is expected to make up for the deficiency of chemotherapy. Most of the research on immunotherapies has been performed on advanced metastatic TNBC, which has provided significant clinical benefits. In the present review, possible immunotherapy targets and ongoing immunotherapy strategies were discussed. In addition, progress in research on immune checkpoint inhibitors in early TNBC was outlined. Contents1. Introduction 2. Breast cancer immune microenvironment 3. Immune checkpoint inhibition 4. Combination of immunotherapy and chemotherapy 5. Other immunotherapies 6. Genomics and immunotherapy 7. Immunotherapy and adverse events 8. Conclusions

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Identification of CTLA-4 associated with tumor microenvironment and competing interactions in triple negative breast cancer by co-expression network analysis

Cited by 36 publications

References 37 publications

Differential Response of MDA-MB-231 and MCF-7 Breast Cancer Cells to In Vitro Inhibition with CTLA-4 and PD-1 through Cancer-Immune Cells Modified Interactions

Differential Response of MDA-MB-231 and MCF-7 Breast Cancer Cells to In Vitro Inhibition with CTLA-4 and PD-1 through Cancer-Immune Cells Modified Interactions

The Characteristics of Tumor Microenvironment in Triple Negative Breast Cancer

Research progress on immunotherapy in triple‑negative breast cancer (Review)

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