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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

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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...
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Tumor Immunotherapy01:27

Tumor Immunotherapy

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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.
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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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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.
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The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
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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.
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Related Experiment Video

Updated: Aug 24, 2025

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
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Target tumor microenvironment by innate T cells.

Yan-Ruide Li1, Matthew Wilson1, Lili Yang1,2,3,4

  • 1Department of Microbiology, Immunology & Molecular Genetics, University of California Los Angeles, Los Angeles, CA, United States.

Frontiers in Immunology
|October 24, 2022
PubMed
Summary

Innate-like T cells, including invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and gamma delta T (γδT) cells, can overcome the immunosuppressive tumor microenvironment (TME) by targeting tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). These cells offer a promising, safer alternative for allogeneic cancer immunotherapy.

Keywords:
cell-based immunotherapygamma delta T (γδT) cellinnate T cellinvariant natural killer T (iNKT) cellmucosal-associated invariant T (MAIT) cellmyeloid-derived suppressor cell (MDSC)tumor microenvironment (TME)tumor-associated macrophage (TAM)

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Area of Science:

  • Immunology
  • Oncology
  • Cell Therapy

Background:

  • The immunosuppressive tumor microenvironment (TME) hinders effective cancer immunotherapy.
  • Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are key components of the TME, impairing immune responses.
  • Novel therapeutic strategies are needed to overcome TME-mediated immunosuppression.

Purpose of the Study:

  • To review the potential of innate-like T cell subsets (iNKT, MAIT, γδT) as a novel immunotherapy for solid-state cancers.
  • To explore the intrinsic anti-TAM/MDSC capacity of these T cells.
  • To evaluate their potential for allogeneic, off-the-shelf cancer immunotherapy.

Main Methods:

  • Review of scientific literature on innate-like T cells and their function in the TME.
  • Analysis of T cell receptor (TCR) and NK activating receptor expression and function.
  • Exploration of chimeric antigen receptor (CAR) engineering for enhanced tumor targeting.

Main Results:

  • Innate-like T cells possess intrinsic capacity to target and eliminate TAMs and MDSCs, thereby remediating the TME.
  • These cells exhibit dual function: direct tumor cell killing and suppression of immunosuppressive myeloid cells.
  • CAR engineering can enhance the tumor-specific targeting of innate-like T cells.
  • Innate-like T cells offer an improved safety profile compared to CAR-T cells, lacking graft-versus-host disease (GvHD) risk.

Conclusions:

  • Innate-like T cells represent a promising therapeutic avenue for overcoming TME-induced immunosuppression in solid tumors.
  • Their ability to target both immunosuppressive cells and tumor cells, combined with an allogeneic safety profile, positions them as potential off-the-shelf cancer immunotherapies.