178. IL-15 Reduces Suppressive Effects of Regulatory T Cells (Tregs) on Antigen-Specific Cytotoxic T Lymphocytes (CTLs)

The aim of the study was to investigate the features of the relation to the number and the phenotype of the cytotoxic T-lymphocytes and NKT-cell from regulatory T-cells content in the blood by patients with renal cell carcinoma. The study included patients with renal cell carcinoma (T3N0M0, clear cell type) at the age of 40-55 years before surgery. Lymphocyte immunophenotyping was performed by flow cytometry. It is found that in the peripheral blood of the patients with renal cell carcinoma accompanied by increased number of T-regulatory cells observed decrease content of the cytotoxic T-lymphocytes and increased levels of the NKT-cells. It is assumed that no change in the number of activated T-regulatory cells and cytotoxic T-lymphocyte determined migration from the blood. Increasing the amount of the NKT-cells in renal cancer is determined by the increase of activated and effector cells but at lower levels of the regulatory subpopulation. The content of the T-regulatory cells in healthy people weakly correlated with the effector subpopulations of T-lymphocytes. In patients with renal cancer the number of the activated T-regulatory cells is closely correlated with the various NKT-lymphocytes fractions. Moreover, if the mature and regulatory NKT-cells subset detected negative relations, so with the NKT-cells expressing CD28 and CD57 markers found positive correlations that characterizes the codirectional dynamics the activated of the regulatory and effector T-lymphocyte subpopulations levels in the background of tumor growth. A canonical analysis demonstrated that the highest significance kidney cancer patients have activated regulatory T-cells, cytotoxic T cells and NKT-cells. A canonical analysis demonstrated that the highest significance by renal cancer patients have activated regulatory T-cells, cytotoxic T-cells and NKT-cells.

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Abstract A100: Downregulation of type 1 interferon receptor (IFNAR1) regulates the balance of regulatory T cells (Tregs) and cytotoxic T lymphocytes (CTLs) in tumor microenvironment

10.1158/2326-6074.tumimm19-a100 ◽

2020 ◽

Author(s):

Hongru Zhang ◽

Jun Gui ◽

Angelica Ortiz ◽

Serge Fuchs

Keyword(s):

T Cells ◽

Tumor Microenvironment ◽

T Lymphocytes ◽

Regulatory T Cells ◽

Cytotoxic T Lymphocytes ◽

Type 1 Interferon ◽

Interferon Receptor

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Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.693215 ◽

2021 ◽

Vol 9 ◽

Author(s):

Runze Qiu ◽

Yue Zhong ◽

Qingquan Li ◽

Yingbin Li ◽

Hongwei Fan

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Tumor Microenvironment ◽

Natural Killer Cells ◽

T Lymphocytes ◽

Regulatory T Cells ◽

Natural Killer ◽

Cytotoxic T Lymphocytes ◽

Glioma Cells ◽

Killer Cells

During metabolic reprogramming, glioma cells and their initiating cells efficiently utilized carbohydrates, lipids and amino acids in the hypoxic lesions, which not only ensured sufficient energy for rapid growth and improved the migration to normal brain tissues, but also altered the role of immune cells in tumor microenvironment. Glioma cells secreted interferential metabolites or depriving nutrients to injure the tumor recognition, phagocytosis and lysis of glioma-associated microglia/macrophages (GAMs), cytotoxic T lymphocytes, natural killer cells and dendritic cells, promoted the expansion and infiltration of immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and conferred immune silencing phenotypes on GAMs and dendritic cells. The overexpressed metabolic enzymes also increased the secretion of chemokines to attract neutrophils, regulatory T cells, GAMs, and dendritic cells, while weakening the recruitment of cytotoxic T lymphocytes and natural killer cells, which activated anti-inflammatory and tolerant mechanisms and hindered anti-tumor responses. Therefore, brain-targeted metabolic therapy may improve glioma immunity. This review will clarify the metabolic properties of glioma cells and their interactions with tumor microenvironment immunity, and discuss the application strategies of metabolic therapy in glioma immune silence and escape.

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Linking tumor-associated macrophages, inflammation, and intestinal tumorigenesis: role of MCP-1

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00252.2012 ◽

2012 ◽

Vol 303 (10) ◽

pp. G1087-G1095 ◽

Cited By ~ 57

Author(s):

Jamie L. McClellan ◽

J. Mark Davis ◽

Jennifer L. Steiner ◽

Reilly T. Enos ◽

Seung H. Jung ◽

...

Keyword(s):

Colon Cancer ◽

T Cells ◽

T Lymphocytes ◽

Regulatory T Cells ◽

Cytotoxic T Lymphocytes ◽

Tumor Associated Macrophages ◽

Intestinal Tissue ◽

Intestinal Tumorigenesis ◽

Polyp Tissue

Tumor-associated macrophages are associated with poor prognosis in certain cancers. Monocyte chemoattractant protein 1 (MCP-1) is thought to be the most important chemokine for recruitment of macrophages to the tumor microenvironment. However, its role on tumorigenesis in a genetic mouse model of colon cancer has not been explored. We examined the role of MCP-1 on tumor-associated macrophages, inflammation, and intestinal tumorigenesis. Male Apc Min/+, Apc Min/+/MCP-1−/− or wild-type mice were euthanized at 18 wk of age and intestines were analyzed for polyp burden, apoptosis, proliferation, β-catenin, macrophage number and phenotype, markers for cytotoxic T lymphocytes and regulatory T cells, and inflammatory mediators. MCP-1 deficiency decreased overall polyp number by 20% and specifically large polyp number by 45% ( P < 0.05). This was consistent with an increase in apoptotic cells ( P < 0.05), but there was no change detected in proliferation or β-catenin. MCP-1 deficiency decreased F4/80-positive cells in both the polyp tissue and surrounding intestinal tissue ( P < 0.05) as well as expression of markers associated with M1 (IL-12 and IL-23) and M2 macrophages (IL-13, CD206, TGF-β, and CCL17) ( P < 0.05). MCP-1 knockout was also associated with increased cytotoxic T lymphocytes and decreased regulatory T cells ( P < 0.05). In addition, MCP-1−/− offset the increased mRNA expression of IL-1β and IL-6 in intestinal tissue and IL-1β and TNF-α in polyp tissue ( P < 0.05), and prevented the decrease in SOCS1 expression ( P < 0.05). We demonstrate that MCP-1 is an important mediator of tumor growth and immune regulation that may serve as an important biomarker and/or therapeutic target in colon cancer.

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