scholarly journals CTLA‑4 blockade combined with 5‑aza‑2'‑deoxycytidine enhances the killing effect of MAGE‑A family common antigen peptide‑specific cytotoxic T cells on breast cancer

2020 ◽  
Author(s):  
Weijing Li ◽  
Meixiang Sang ◽  
Xiaoguang Hao ◽  
Yunyan Wu ◽  
Baoen Shan
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cytotoxic T Cells ◽  
Common Antigen ◽  
Killing Effect ◽  
Antigen Peptide

scholarly journals Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

2021 ◽  
Author(s):  
H. Kuroda ◽  
T. Jamiyan ◽  
R. Yamaguchi ◽  
A. Kakumoto ◽  
A. Abe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Associated Macrophages ◽  
Free Survival ◽  
Infiltrating Lymphocytes

Abstract Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.

Thyroid status regulates tumor microenvironment delineating breast cancer fate

2021 ◽  
Author(s):  
Helena Andrea Sterle ◽  
Ximena Hildebrandt ◽  
Matías Valenzuela Álvarez ◽  
María Alejandra Paulazo ◽  
Luciana Mariel Gutierrez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Lung Metastasis ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Thyroid Status ◽  
Cd8 Cells ◽  
Regulatory T Lymphocytes ◽  
Starting Point

The patient’s hormonal context plays a crucial role in the outcome of cancer. However, the association between thyroid disease and breast cancer risk remains unclear. We evaluated the effect of thyroid status on breast cancer growth and dissemination in an immunocompetent mouse model. For this, hyperthyroid and hypothyroid Balb/c mice were orthotopically inoculated with triple negative breast cancer 4T1 cells. Tumors from hyperthyroid mice showed increased growth rate and an immunosuppressive tumor microenvironment, characterized by increased IL-10 levels and decreased percentage of activated cytotoxic T cells. On the other hand, a delayed tumor growth in hypothyroid animals was associated with increased tumor infiltration of activated CD8+ cells and a high IFNγ/IL-10 ratio. Paradoxically, hypothyroid mice developed a higher number of lung metastasis than hyperthyroid animals. This was related to an increased secretion of tumor CCL2 and an immunosuppressive systemic environment, with increased proportion of regulatory T cells and IL-10 levels in spleens. A lower number of lung metastasis in hyperthyroid mice was related to the reduced presence of mesenchymal stem cells in tumors and metastatic sites. These animals also exhibited decreased percentages of regulatory T lymphocytes and myeloid-derived suppressor cells in spleens, but increased activated CD8+ cells and IFNγ/IL-10 ratio. Therefore, thyroid hormones modulate the cellular and cytokine content of the breast tumor microenvironment. The better understanding of the mechanisms involved in these effects could be a starting point for the discovery of new therapeutic targets for breast cancer.

scholarly journals Cytotoxic T cells response with decreased CD4/CD8 ratio during mammary tumors inhibition in rats induced by non-contact electric fields

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 35
Author(s):  
Firman Alamsyah ◽  
Rarastoeti Pratiwi ◽  
Nisrina Firdausi ◽  
Jessica Irene Mesak Pello ◽  
Subekti Evi Dwi Nugraheni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Electric Fields ◽  
Mammary Tumor ◽  
Caspase 3 ◽  
Cytotoxic T Cells ◽  
Mammary Tumors ◽  
Intermediate Frequency ◽  
Surrounding Tissue ◽  
Novel Therapy

Background: Breast cancer is the most common cancer in women worldwide and is the leading cause of death in women with cancer. One novel therapy used for breast cancer treatment is non-contact electric fields called electro-capacitive cancer therapy (ECCT) with intermediate frequency (100 kHz) and low intensity (18 Vpp). The objective of this study was to examine the effect of ECCT on mammary tumors growth in rats and observing the immune responses that play a role in fighting the tumor. Methods: Female SD rats were used and divided into four groups, namely control (NINT), placebo (NIT), non- therapy (INT), and therapy (IT) groups with 6 biological replicates in each group. Rats in INT and IT groups were treated with 7,12-dimethylbenz[a]anthracene for mammary tumor induction. Only rats in NIT and IT groups were exposed to ECCT individually for 10 hours per day for 21 days. The size of all tumors was measured with a digital caliper. The distributions of PCNA, ErbB2, caspase-3, CD68, CD4 and CD8-positive cells were observed with immunohistochemistry and scoring with ImageJ. Results: The growth rate of mammary tumors in IT group was significantly lower (p<0.05) than that in the INT group. The number of mitotic figures and the percentage of PCNA, caspase-3, and CD68- positive cells in IT group were significantly lower (p<0.05) than those in INT group. Conversely, the percentage of CD8-positive T cells in IT group was significantly higher (p<0.05) than that in INT group. Moreover, the CD4/CD8 ratio in IT group was decreased. Some tumor tissues were blackened and detached from the surrounding tissue, resulting in an open wound which then healed up upon exposure. Conclusions: Non-contact electric fields exposure showed inhibition on mammary tumor growth in rats while inducing CD8+ T cells that lead to tumor cells death and potentially helps wound healing.

scholarly journals Autologous dendritic cells and activated cytotoxic T‑cells as combination therapy for breast cancer

2019 ◽  
Author(s):  
Julia Shevchenko ◽  
Alexander Khristin ◽  
Vasily Kurilin ◽  
Maria Kuznetsova ◽  
Darya Blinova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Combination Therapy ◽  
Cytotoxic T Cells

scholarly journals To explore immune synergistic function of Quercetin in inhibiting breast cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dan Qiu ◽  
Xianxin Yan ◽  
Xinqin Xiao ◽  
Guijuan Zhang ◽  
Yanqiu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Γδ T Cells ◽  
Killing Effect ◽  
Protein Levels ◽  
Stat1 Signaling ◽  
Mcf 7

Abstract Background The precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class of nontraditional T cells that have long attracted attention due to their potential in immunotherapy. In this study, we revealed the immunomodulatory function of Que through regulation of the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells. Methods In the experimental design, we first screened target genes with or without Que treatment, and we intersected the Que target with the disease target by functional enrichment analysis. Second, MCF-10A, MCF-10AT, MCF-7 and MDA-MB-231 breast cancer cell lines were treated with Que for 0 h, 24 h and 48 h. Then, we observed the expression of its subsets by coculturing Que and γδ T cells and coculturing Que and γδ T cells with breast tumor cells to investigate their synergistic killing effect on tumor cells. Finally, Western blotting was used to reveal the changes in proteins related to the JAK/STAT1 signaling pathway after Que treatment in MCF-10AT and MCF-7 cells for 48 h. Results The pathway affected by Que treatment was the JAK/STAT1 signaling pathway and was associated with precancerous breast cancer, as shown by network pharmacology analysis. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 cells in a time- and concentration-dependent manner (P < 0.05). Most importantly, Que promoted the differentiation of γδ T cells into the Vδ2 T cell subpopulation. The best ratio of effector cells to target cells (E/T) was 10:1, the killing percentages of γδ T cells against MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 were 61.44 ± 4.70, 55.52 ± 3.10, 53.94 ± 2.74, and 53.28 ± 1.73 (P = 0.114, P = 0.486, and P = 0.343, respectively), and the strongest killing effect on precancerous breast cancer cells and breast cancer cells was found when the Que concentration was 5 μM and the E/T ratio was 10:1 (64.94 ± 3.61, 64.96 ± 5.45, 55.59 ± 5.98, and 59.04 ± 5.67, respectively). In addition, our results showed that Que increased the protein levels of IFNγ-R, p-JAK2 and p-STAT1 while decreasing the protein levels of PD-L1 (P < 0.0001). Conclusions In conclusion, Que plays a synergistic role in killing breast cancer cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1 and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of breast cancer.

scholarly journals A Polysaccharide From the Whole Plant of Plantago asiatica L. Enhances the Antitumor Activity of Dendritic Cell-Based Immunotherapy Against Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiafeng Gao ◽  
Yi-Nan Zhang ◽  
Jingwen Cui ◽  
Jiatong Zhang ◽  
Yuexiang Ming ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Breast Tumor ◽  
Cytotoxic T Cells ◽  
Tumor Model ◽  
Whole Plant ◽  
Plantago Asiatica ◽  
Breast Tumor Model

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) that mediate T-cell immune responses. Breast cancer is one of the most commonly diagnosed diseases and its mortality rate is higher than any other cancer in both humans and canines. Plantain polysaccharide (PLP), extracted from the whole plant of Plantago asiatica L., could promote the maturation of DCs. In this research, we found that PLP could upregulate the maturation of DCs both in vitro and in vivo. PLP-activated DCs could stimulate lymphocytes’ proliferation and differentiate naive T cells into cytotoxic T cells. Tumor antigen-specific lymphocyte responses were enhanced by PLP and CIPp canine breast tumor cells lysate-pulsed DCs, and PLP and CIPp-cell-lysate jointly stimulated DCs cocultured with lymphocytes having the great cytotoxicity on CIPp cells. In the 4T1 murine breast tumor model, PLP could control the size of breast tumors and improve immunity by recruiting DCs, macrophages, and CD4+ and CD8+ T cells in the tumor microenvironment. These results indicated that PLP could achieve immunotherapeutic effects and improve immunity in the breast tumor model.

Human Multiple Myeloma and Breast Cancer Cells Evade Immune Rejection Through Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2942-2942
Author(s):  
Mathias Witzens-Harig ◽  
Dirk Hose ◽  
Simone Jünger ◽  
Christina Pfirschke ◽  
Nisit Khandelwal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Adhesion Molecule ◽  
Cytotoxic T Cells ◽  
Cd8 T Cell ◽  
Related Cell

Abstract Abstract 2942 Tumor-specific cytotoxic T cells are common in tumor patients, but ineffectively react against autologous tumor cells. Here, we demonstrate in multiple myeloma and breast cancer that human tumor cells escape recognition by tumor-specific CD8+ T cells through carcinoembryonic antigen-related cell adhesion molecule-6 (CEACAM-6) expression. We demonstrate for the first time CEACAM-6 expression in primary and established myeloma and examined the effects of altered CEACAM expression on cytotoxic T cell activity and cytokine secretion against myeloma and breast cancer cells in vitro —, and in vivo, using a xenotransplant mouse model. Cytotoxic T cells from multiple myeloma patients reacted against myeloma antigens presented by dendritic cells, but not against autologous myeloma cells, which expressed CEACAM6. Gene knockdown or blocking of CEACAM6 on myeloma cells restored CD8+ T-cell reactivity against malignant plasma cells. SiRNA-mediated CEACAM6 knockdown or inhibition by specific mAbs also restored cytokine secretion, cytotoxic activity, and antigen-specific lysis of CEACAM6-positive breast cancer cells. Moreover, CEACAM-6 inhibition was a prerequisite for efficient treatment of xenotransplanted breast tumors by adoptive T cell transfer. CEACAM6 thus plays an important role in inhibiting CD8+ T-cell responses against hematological and epithelial human tumors. Therapeutic targeting of CEACAM6 may be a promising strategy for improving cancer immunotherapy. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document