scholarly journals A novel potential effective strategy for enhancing the antitumor immune response in breast cancer patients using a viable cancer cell‑dendritic cell‑based vaccine

2018 ◽  
Author(s):  
Mona Abdellateif ◽  
Sabry Shaarawy ◽  
Eman Kandeel ◽  
Ahmed El‑Habashy ◽  
Mohamed Salem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Dendritic Cell ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Antitumor Immune Response ◽  
Effective Strategy ◽  
Breast Cancer Patients ◽  
Viable Cancer Cell ◽  
Dendritic Cell Based Vaccine

scholarly journals The relationship of GITR, Lag-3 and PD-1 expression with the main indicators of systemic and local immunity in patients with breast cancer

2021 ◽  
Vol 23 (3) ◽  
pp. 457-465
Author(s):  
Dmitrii V. Tabakov ◽  
Tatiana N. Zabotina ◽  
Naily V. Chanturia ◽  
Elena N. Zakharova ◽  
Igor K. Vorotnikov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Tumor Tissue ◽  
Antitumor Immune Response ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Cd11b Expression ◽  
Local Immunity

Background. To enhance the antitumor immune response, new promising methods of immunotherapy are being developed. They consist in the blockade and activation of immune check-point molecules, in particular, the blockade of the Lag‐3 molecule (lymphocyte-activation gene 3) and the activation of the GITR receptor (Glucocorticoid induced TNF receptor). In the studies of combined use with PD-1 blockers, encouraging results were obtained, which makes the assessment of the expression of Lag-3 and GITR on immunocompetent cells of peripheral blood (PB) and tumor tissue necessary for the personalization of such treatment and understanding of the mechanisms of the antitumor immune response. Materials and methods. The study included peripheral blood samples and surgical material from 39 breast cancer patients being treated at the Blokhin National Medical Research Center of Oncology. The subpopulation composition and expression of PD-1, Lag-3, and GITR molecules were evaluated by flow cytometry. Results. The analysis of the main populations of PB lymphocytes showed that in patients with breast cancer, the content of NKT-lymphocytes was increased, and the proportions of lymphocytes expressing CD11b and CD25 markers were increased compared to the donor group. It was revealed that the tumor tissue is dominated by T-cells, an increase in the proportion of which occurs due to a reduced content of NK-lymphocytes and B-lymphocytes. The structure of Tumor-infiltrating lymphocytes (TILs) is dominated by subpopulations with immunosuppressive activity, which is indicated by a decrease in the content of CD11b+, CD25+ and perforin-positive cells, increased expression of Lag-3 and PD-1. For PB and tumor tissue, the average degree of dependence of Lag-3 expression on the content of PD-1+ lymphocytes was shown. There is an increase in the content of immunosuppressive subpopulations with high PD-1 values in PB and TILs. The direct dependence of the number of perforin-containing lymphocytes and CD11b expression on the GITR content in the PB was established, but it is not typical for breast cancer tissue. Conclusion. Since the blockade of the Lag-3 molecule by monoclonal antibodies can enhance the effect of anti-PD-1 therapy in cancer patients, it is necessary to evaluate the expression and co-expression of these two markers. A high content of GITR-positive lymphocytes in the tumor tissue, on the one hand, and a decrease in the proportion of effector subpopulations of lymphocytes, on the other, indicates the influence of the tumor microenvironment on the functioning of GITR-mediated activation of the immune response. Further investigation of GITR expression and functional activity is required to understand the nature of this contradiction.

scholarly journals MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

2021 ◽  
Vol 22 (10) ◽  
pp. 5382
Author(s):  
Pei-Yi Chu ◽  
Hsing-Ju Wu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Protein Expression ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Expression Ratio

(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan–Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer.

scholarly journals Effect of yoga on sleep quality and neuroendocrine immune response in metastatic breast cancer patients

2017 ◽  
Vol 23 (3) ◽  
pp. 253 ◽  
Author(s):  
RaghavendraMohan Rao ◽  
HS Vadiraja ◽  
R Nagaratna ◽  
KS Gopinath ◽  
Shekhar Patil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Metastatic Breast Cancer ◽  
Sleep Quality ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients

scholarly journals Tumor Heterogeneity Correlates with Less Immune Response and Worse Survival in Breast Cancer Patients

2019 ◽  
Vol 26 (7) ◽  
pp. 2191-2199 ◽  
Author(s):  
Kerry-Ann McDonald ◽  
Tsutomu Kawaguchi ◽  
Qianya Qi ◽  
Xuan Peng ◽  
Mariko Asaoka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Cancer Patients ◽  
Tumor Heterogeneity ◽  
Breast Cancer Patients
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