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Updated: Jan 20, 2026

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
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Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

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Can Allosteric Receptor-Protein Interactions in Receptor Complexes Be a Molecular Mechanism Involved in Cancer Immune

Dasiel O Borroto-Escuela1,2,3, Kjell Fuxe1

  • 1Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Frontiers in Endocrinology
|September 5, 2019
PubMed

Insights

A novel allosteric mechanism involving receptor-receptor interactions in immune cells may explain how cancer evades the immune system. This interaction involving CTLA-4, PD-1, and adenosine A2AR can inhibit T cell activation, blocking cancer immunotherapy.

Area of Science:

  • Immunology
  • Molecular Biology
  • Neuroscience

Background:

  • Allosteric receptor-receptor interactions are key in the central nervous system.
  • These interactions regulate synaptic and extrasynaptic signaling.
  • Their role in immunological synapses is not well understood.

Purpose of the Study:

  • To propose a similar allosteric receptor-receptor interaction mechanism in immunological synapses.
  • To investigate the role of CTLA-4, PD-1, and adenosine A2AR in T cell inhibition and cancer development.
  • To understand how these interactions impact T cell receptor (TCR) signaling and cancer immunotherapy.

Main Methods:

  • Theoretical discussion based on existing literature and discoveries in neuroscience.
  • Analysis of potential molecular mechanisms in T cell signaling.
  • Hypothesizing the formation and function of heteroreceptor complexes in immunological synapses.

Main Results:

  • A proposed mechanism where CTLA-4, PD-1, and adenosine A2AR form heteroreceptor complexes within the immunological synapse.
  • These complexes can exert inhibitory control over T cell activation by interacting with the T cell receptor (TCR) and its accelerators.
  • Imbalance in these complexes, favoring inhibitory signals, can lead to tumor-induced immunosuppression.

Conclusions:

  • Allosteric receptor-receptor interactions represent a significant regulatory mechanism in immunological synapses.
  • This mechanism provides a molecular basis for how tumors induce immunosuppression and resist immunotherapy.
  • Targeting these inhibitory complexes could offer new strategies for enhancing cancer immunotherapy.
Keywords:
A2AR-TCR heteroreceptor complexesT cellallosteric receptor-receptor interactionscancer immunotherapyimmunosuppression

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