Related Experiment Video

Updated: Jun 5, 2026

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
10:13

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Published on: May 6, 2019

Defining the mechanisms of CD8 T-cell tumor tolerance

Benjamin C Kennedy1, Shinji Shimato, Richard Ce Anderson

  • 1Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA. benjamin.c.kennedy@gmail.com

Immunotherapy
|December 23, 2010
PubMed

Insights

Tumors evade immune responses by myeloid-derived suppressor cells (MDSCs) inhibiting CD8 T-cells. MDSCs nitrate T-cell receptors (TCRs), suppressing tumor-specific responses while sparing others, offering new therapeutic targets in tumor immunology.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Tumor evasion of immune surveillance is a critical challenge in cancer.
  • Myeloid-derived suppressor cells (MDSCs) are known to inhibit T-cell responses, but the precise mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the specific mechanisms by which MDSCs inhibit CD8 T-cell function in the tumor microenvironment.
  • To identify how MDSCs selectively suppress T-cell receptor (TCR) signaling.

Main Methods:

  • Investigated the interaction between MDSCs and CD8 T-cells in a tumor model.
  • Analyzed the molecular modifications of the TCR complex upon MDSC exposure.
  • Assessed T-cell activation, proliferation, and cytokine production in response to specific antigens.

Main Results:

  • MDSCs selectively suppress CD8 T-cells specific to tumor antigens, leaving responses to other antigens intact.
  • MDSCs induce nitration of the TCR complex, disrupting TCR/CD3ζ and TCR/CD8 interactions.
  • This leads to reduced TCR signaling, impaired T-cell activation, proliferation, and interferon-gamma (IFN-γ) production.

Conclusions:

  • MDSC-mediated CD8 T-cell inhibition is antigen-specific and occurs via nitration of the TCR complex.
  • This mechanism provides crucial insights into tumor immune evasion.
  • Identifies potential therapeutic targets for enhancing anti-tumor immunity.

More Related Videos

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

Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells09:57

Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells

Published on: January 29, 2019

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...
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...
Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
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...
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.