Related Experiment Video

Updated: Nov 10, 2025

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
07:36

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

Published on: June 12, 2021

7.1K

CD8+ T cells inhibit metastasis and CXCL4 regulates its function

Robiya Joseph1, Rama Soundararajan1, Suhas Vasaikar1

  • 1Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

British Journal of Cancer
|April 2, 2021
PubMed
Abstract

Insights

Immune cells, specifically CD8+ T cells, inhibit cancer metastasis. However, platelets and CXCL4 can promote metastasis by generating myeloid-derived suppressor cells that suppress CD8+ T cell activity, impacting patient survival.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Metastasis

Background:

  • The precise mechanisms by which immune cells influence cancer metastasis remain poorly understood.
  • Elucidating the role of immune cells in metastasis is crucial for developing novel therapeutic strategies to enhance patient survival.

Purpose of the Study:

  • To investigate the interplay between immune cells, platelets, and metastasis in tumor progression.
  • To identify key molecular players and cellular interactions that regulate the metastatic process.

Main Methods:

  • Utilized syngeneic orthotopic mouse tumor models, including knockout variants (CD8, CD4) and immunodeficient mice.
  • Administered CXCL4 and analyzed tumors and lungs for cancer cell dissemination via bioluminescence.
  • Isolated circulating tumor cells and performed immunohistochemistry on mouse tumors and a human triple-negative breast cancer (TNBC) tissue microarray.
  • Analyzed The Cancer Genome Atlas (TCGA) pan-cancer data from over 10,000 patients.

Main Results:

  • Discovered distinct intratumoral immune infiltration patterns in metastatic versus non-metastatic tumors.
  • Non-metastatic tumors exhibited high CD8+ T cell and low platelet levels, with the inverse observed in metastatic tumors.
  • Platelets and CXCL4 were shown to induce monocyte differentiation into myeloid-derived suppressor cells (MDSCs), which suppress CD8+ T cell function during tumor progression.
  • TCGA data analysis revealed significantly lower survival probability in patients with CD8lowPlatelethigh profiles compared to CD8highPlateletlow profiles.

Conclusions:

  • CD8+ T cells play a critical role in inhibiting cancer metastasis.
  • Disruption of the balance between CD8+ T cells and platelets leads to CXCL4 production by platelets, inducing MDSCs and consequently inhibiting CD8+ T cell-mediated anti-metastatic activity.

More Related Videos

Author Spotlight: A Model to Study the Systemic and Local Dynamics of CD8+ T Cells During LN Metastasis07:45

Author Spotlight: A Model to Study the Systemic and Local Dynamics of CD8+ T Cells During LN Metastasis

Published on: January 26, 2024

2.3K
Experimental Metastasis and CTL Adoptive Transfer Immunotherapy Mouse Model08:06

Experimental Metastasis and CTL Adoptive Transfer Immunotherapy Mouse Model

Published on: November 26, 2010

19.9K

Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
13.8K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
5.8K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.2K
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...
1.7K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.0K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.2K