CTLA-4 Expression and Its Clinical Significance in Breast Cancer

Kern, Rodrigo

doi:10.1007/s00005-021-00618-5

Cited by 30 publications

(24 citation statements)

References 68 publications

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“…We also observed high expression of the immune checkpoint regulator CTLA-4 in breast tumor infiltrates from the exposed patients. Literature reports some associations between CTLA-4 expression in the tumor microenvironment and worse outcomes [ 34 ], reaching more than 50% of cases [ 35 ]. Even though we did not find any specific study about the impact of pesticides on CTLA-4 expression and considering the IL-12 and TGF-β1-induced changes, exposure to such substances significantly affects the negative regulation of the immune environment of breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Occupational Exposure to Pesticides Affects Pivotal Immunologic Anti-Tumor Responses in Breast Cancer Women from the Intermediate Risk of Recurrence and Death

Silva

Scandolara

Kern

et al. 2022

Cancers

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Breast cancer risk stratification is a strategy based using on clinical parameters to predict patients’ risk of recurrence or death, categorized as low, intermediate, or high risk. Both low and high risk are based on well-defined clinical parameters. However, the intermediate risk depends on more malleable parameters. It means an increased possibility for either suboptimal treatment, leading to disease recurrence, or systemic damage due to drug overload toxicity. Therefore, identifying new factors that help to characterize better the intermediate-risk stratification, such as environmental exposures, is necessary. For this purpose, we evaluated the impact of occupational exposure to pesticides on the systemic profile of cytokines (IL-12, IL-4, IL-17A, and TNF-α) and oxidative stress (hydroperoxides, total antioxidants, and nitric oxide metabolites), as well as TGF-β1, CTLA-4, CD8, and CD4 expression, investigated in tumor cells. Occupational exposure to pesticides decreased the levels of IL-12 and significantly increased the expression of TGF-β1 and CTLA-4 in the immune infiltrate. Nevertheless, we observed a decrease in CTLA-4 in tumor samples and CD8 in infiltrating cells of intermediate overweight or obese patients with at least one metastatic lymph node at the diagnosis. These findings indicate that occupational exposure to pesticides changes the molecular behavior of disease and should be considered for intermediate-risk stratification assessment in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Occupational Exposure to Pesticides Affects Pivotal Immunologic Anti-Tumor Responses in Breast Cancer Women from the Intermediate Risk of Recurrence and Death

Silva

Scandolara

Kern

et al. 2022

Cancers

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“…CTLA-4 is an essential stimulatory receptor that regulates T-cell activation, which can reduce or eliminate immune cell function and encourage tumor cells to escape immune surveillance. Inhibition of CTLA-4 can eliminate immune tolerance and tumor cell proliferation ( Kern and Panis, 2021 ). The TMB represents the number of mutations per megabase (Mut/Mb) in specific cancer.…”

Section: Discussionmentioning

confidence: 99%

A novel lactate metabolism-related signature predicts prognosis and tumor immune microenvironment of breast cancer

Zhang

Fang

2022

Front. Genet.

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Background: Lactate, an intermediate product of glycolysis, has become an essential regulator of tumor maintenance, development, and metastasis. Lactate can drive tumors by changing the microenvironment of tumor cells. Because of lactate’s important role in cancer, we aim to find a novel prognostic signature based on lactate metabolism-related genes (LMRGs) of breast cancer (BC).Methods: RNA-sequencing data and clinical information of BC were enrolled from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We obtained LMRGs from the Molecular Signature Database v7.4 and articles, and then we compared candidate genes with TCGA data to get differential genes. Univariate analysis and most minor absolute shrinkage and selector operator (LASSO) Cox regression were employed to filter prognostic genes. A novel lactate metabolism-related risk signature was constructed using a multivariate Cox regression analysis. The signature was validated by time-dependent ROC curve analyses and Kaplan–Meier analyses in TCGA and GEO cohorts. Then, we further investigated in depth the function of the model’s immune microenvironment.Results: We constructed a 3-LMRG-based risk signature. Kaplan–Meier curves confirmed that high-risk score subgroups had a worse prognosis in TCGA and GEO cohorts. Then a nomogram to predict the probability of survival for BC was constructed. We also performed Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway function analysis. The function analysis showed that the lactate metabolism-related signature was significantly related to immune response. A significant correlation was observed between prognostic LMRGs and tumor mutation burden, checkpoints, and immune cell infiltration. An mRNA–miRNA network was built to identify an miR-203a-3p/LDHD/LYRM7 regulatory axis in BC.Conclusion: In conclusion, we constructed a novel 3-LMRG signature and nomogram that can be used to predict the prognosis of BC patients. In addition, the signature is closely related to the immune microenvironment, which may provide new insight into future anticancer therapies.

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“…However, flow cytometry is faster and easier. Previous studies have shown that CTLA-4 expression levels are elevated in breast cancer patients [ 33 ], and the absence of CTLA-4 can cause dysregulation of the immune response [ 34 ]. Peng Pu-ji et al found that TIM-3 was highly expressed in pancreatic cancer tissues [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Occupational Low-Dose Radiation Affects the Expression of Immune Checkpoint of Medical Radiologists

Wang

Hao

Dai

et al. 2022

IJERPH

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The purpose of this study was to investigate the expression of immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T cell immunoglobulin and mucin domain 3 (TIM-3) in the peripheral blood T lymphocytes of medical radiologists. The study incorporated 100 male medical radiologists and 107 male healthy controls. The expressions of CTLA-4 and TIM-3 among CD4+ and CD8+ lymphocytes were detected by flow cytometry. The expression levels of CTLA-4 and TIM-3 in the CD4+T cells of radiation workers were lower than those of healthy controls (p < 0.05). Correlation analysis showed that the CD8+CTLA-4 expression level was significantly positively correlated with individual cumulative dose (rs = 0.260, p = 0.001, <0.05), while the expression level of CD8+TIM-3 was negatively correlated (rs = −0.180, p = 0.027, <0.05). Low-dose radiation exposure affects the expression of CTLA-4 and TIM-3 in human peripheral blood T lymphocytes. Future studies need to focus on exploring the mechanisms by which CTLA-4 and TIM-3 expression changes in response to low-dose radiation exposure.

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CTLA-4 Expression and Its Clinical Significance in Breast Cancer

Cited by 30 publications

References 68 publications

Occupational Exposure to Pesticides Affects Pivotal Immunologic Anti-Tumor Responses in Breast Cancer Women from the Intermediate Risk of Recurrence and Death

Occupational Exposure to Pesticides Affects Pivotal Immunologic Anti-Tumor Responses in Breast Cancer Women from the Intermediate Risk of Recurrence and Death

A novel lactate metabolism-related signature predicts prognosis and tumor immune microenvironment of breast cancer

Occupational Low-Dose Radiation Affects the Expression of Immune Checkpoint of Medical Radiologists

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