Related Experiment Video

Updated: Nov 26, 2025

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
08:41

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity

Published on: June 7, 2017

8.5K

Regulatory T Cells Support Breast Cancer Progression by Opposing IFN-γ-Dependent Functional Reprogramming of Myeloid

Nicholas M Clark1, Leandro M Martinez2, Steven Murdock2

  • 1Department of Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA; Integrative Life Sciences Graduate Program, Virginia Commonwealth University, Richmond, VA 23298, USA.

Cell Reports
|December 9, 2020
PubMed

Insights

Regulatory T (Treg) cells hinder anti-tumor immunity in breast cancer. Their ablation unleashes inflammatory monocytes that become tumor-associated macrophages (TAMs), promoting tumor suppression via IFN-γ signaling.

Area of Science:

  • Immunology
  • Cancer Biology
  • Tumor Microenvironment

Background:

  • Regulatory T (Treg) cells infiltrate solid tumors, correlating with poor prognosis, but their tumor-suppressive mechanisms remain unclear.
  • Understanding Treg cell function is crucial for developing effective cancer immunotherapies.

Purpose of the Study:

  • To elucidate the mechanisms by which Treg cell ablation mediates anti-tumor effects in murine breast cancer.
  • To investigate the role of myeloid cells, specifically monocytes and macrophages, in Treg cell-mediated tumor suppression.

Main Methods:

  • Utilized transgenic mice models for Treg cell ablation and cell fate mapping.
  • Employed adoptive transfer and co-injection strategies to study immune cell interactions within the tumor microenvironment.
  • Performed transcriptomic analysis of tumor-associated macrophages (TAMs) under different experimental conditions.

Main Results:

  • Treg cell ablation-dependent anti-tumor effects require the recruitment of CCR2+ inflammatory monocytes into the tumor.
  • These monocytes differentiate into TAMs, whose function is reprogrammed in an IFN-γ-dependent manner.
  • Transcriptomic signatures of TAMs in Treg-ablated tumors correlate with improved survival in human breast cancer patients.

Conclusions:

  • Breast cancer progression is highly dependent on myeloid cell function.
  • IFN-γ signaling in monocytes plays a critical role in Treg cell-mediated anti-tumor immunity.
  • Targeting the IFN-γ pathway in monocytes represents a potential therapeutic strategy for breast cancer.
Keywords:
breast cancerinterferon gammamonocytesregulatory T cellstumor-associated macrophages

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.2K
Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice07:36

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

7.2K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.2K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.8K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
9.7K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.6K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
888
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.9K