Related Experiment Video

Updated: Feb 15, 2026

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
16:24

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

20.7K

TIM-3 Regulates CD103+ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer

Álvaro de Mingo Pulido1, Alycia Gardner2, Shandi Hiebler1

  • 1Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive SRB-2, Tampa, FL 33612, USA.

Cancer Cell
|January 10, 2018
PubMed

Insights

Targeting TIM-3 (T-cell immunoglobulin and mucin-domain containing-3) enhances breast cancer chemotherapy. Blocking TIM-3 improved paclitaxel efficacy in triple-negative and luminal B models by boosting CD8+ T-cell responses.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Intratumoral CD103+ dendritic cells (DCs) are crucial for initiating anti-tumor immunity.
  • Identifying immune regulators on these DCs can reveal therapeutic targets for breast cancer.

Purpose of the Study:

  • To evaluate immune regulator expression on CD103+ DCs in a murine breast cancer model.
  • To investigate TIM-3 as a potential therapeutic target in combination with chemotherapy.

Main Methods:

  • Analysis of immune regulator expression on CD103+ DCs in a murine breast cancer model.
  • Assessment of anti-TIM-3 antibody efficacy combined with paclitaxel in triple-negative and luminal B breast cancer models.
  • Evaluation of CD8+ T-cell dependency, granzyme B expression, and Cxcl9/CXCR3 pathway involvement.

Main Results:

  • TIM-3 expression was identified on CD103+ DCs and predominantly on myeloid cells in tumors.
  • Anti-TIM-3 antibody combined with paclitaxel improved treatment response without toxicity.
  • Therapeutic efficacy was dependent on CD8+ T cells and associated with increased granzyme B.
  • Combination therapy upregulated Cxcl9 in intratumoral DCs, and efficacy was lost with CXCR3 blockade or Batf3/Irf8 deficiency.

Conclusions:

  • TIM-3 is a viable therapeutic target for enhancing breast cancer chemotherapy, particularly in combination regimens.
  • The anti-tumor effect of combined anti-TIM-3 and paclitaxel therapy is mediated by CD8+ T cells via the Cxcl9/CXCR3 axis.
  • Targeting TIM-3 offers a promising strategy to improve immunotherapy outcomes in specific breast cancer subtypes.

Keywords:
TIM-3breast cancerchemotherapydendritic cellsgalectin-9immunotherapypaclitaxel

More Related Videos

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells09:32

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells

Published on: February 8, 2018

15.6K
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples07:03

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples

Published on: October 2, 2020

5.1K

Related Concept Videos

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
715
Testosterone: Functions and Regulation01:26

Testosterone: Functions and Regulation

The intricate hormonal interplay essential for male reproductive health begins with the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus. This hormone prompts the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). LH targets the Leydig cells in the testes, stimulating them to produce and release testosterone. In concert with testosterone, FSH acts on the Sertoli cells within the seminiferous tubules to facilitate the release of...
2.4K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K
pH Regulation in Cells01:28

pH Regulation in Cells

pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
7.8K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.9K