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Related Concept Videos

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.
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...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
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...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...

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Related Experiment Video

Updated: Jun 26, 2026

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells

Published on: September 23, 2021

Small Molecule Activators of Antitumor Immunity.

Vaibhav Pal Singh1, Motonari Uesugi1,2

  • 1Division of Biochemistry, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.

Accounts of Chemical Research
|June 24, 2026
PubMed
Summary

Chemical strategies can restore T-cell function for cancer immunotherapy. Small molecules like arvenin I and spermidine mimetics revive exhausted T-cells and enhance antitumor immunity, especially in aged hosts.

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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
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Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
09:04

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

Area of Science:

  • Chemical biology
  • Cancer immunotherapy
  • Immunology

Background:

  • Immune checkpoint blockade therapies show promise but are limited by dysfunctional T-cells in the tumor microenvironment.
  • Aged hosts exhibit impaired immune fitness and reduced responsiveness to PD-1/PD-L1 therapies due to metabolic and signaling deficits.
  • Chemical modulation of immune cell function offers a strategy to overcome these limitations.

Purpose of the Study:

  • To explore the use of small molecules to restore T-cell activity and enhance antitumor immunity.
  • To identify chemical mechanisms that can synergize with immune checkpoint blockade.
  • To develop strategies to overcome age-associated immune dysfunction in cancer therapy.

Main Methods:

  • Cell-based screening and electrophile-focused chemoproteomics to identify small-molecule modulators.
  • Profiling of spermidine-interacting proteins using chemoproteomic tools.
  • In vivo assessment of identified small molecules for restoring mitochondrial fitness and enhancing antitumor immunity.

Main Results:

  • Identification of arvenin I, a covalent activator of MKK3, which revives exhausted T-cells and synergizes with immune checkpoint blockade.
  • Discovery that age-associated spermidine depletion impairs T-cell metabolism and checkpoint blockade response.
  • Identification of a biostable spermidine mimetic that restores mitochondrial function and enhances in vivo antitumor immunity.

Conclusions:

  • A chemical biology framework combining covalent signaling activation and metabolite-inspired energy support can restore T-cell fitness.
  • Chemoproteomic discovery can guide the development of novel immune-activating small molecules.
  • Chemical approaches hold significant potential to complement and extend the efficacy of cancer immunotherapy, particularly in aged individuals.