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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

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Low Avidity T Cells Do Not Hinder High Avidity T Cell Responses Against Melanoma.

Kalliopi Ioannidou¹, Olivier Randin¹, Aikaterini Semilietof¹

¹Department of Oncology, Lausanne University Hospital Center (CHUV), Lausanne, Switzerland.

Frontiers in Immunology

|September 27, 2019

Summary

Low avidity CD8 T cells do not hinder high avidity T cells. This study found that low avidity T cells do not impede anti-tumor responses, which is reassuring for natural T cell immunity.

Keywords:

IFN-γ Elispot assay T cell response adoptive T cell transfer avidity cytotoxicity assay melanoma

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Area of Science:

Immunology
Cancer Immunology
T cell biology

Background:

T cell efficacy relies on functional avidity, the strength of T cell-antigen interaction.
Tumor antigen-specific CD8 T cell responses involve clonotypes with varying functional avidities.
A recent hypothesis suggested low avidity T cells might impair high avidity T cells against tumors.

Purpose of the Study:

To investigate the impact of low avidity CD8 T cells on high avidity T cell function.
To analyze human cytotoxic CD8 T cells targeting the melanoma antigen Melan-A/MART-1.

Main Methods:

Analysis of human cytotoxic CD8 T cells specific for Melan-A/MART-1.
Assessment of T cell cytotoxicity and cytokine production.
In vivo studies using NSG-HLA-A2 mice to evaluate anti-tumor effects.

Main Results:

The presence of low avidity T cells did not reduce the cytotoxicity of high avidity T cells.
High avidity T cells maintained cytokine production regardless of low avidity T cell presence.
In vivo anti-tumor effects of high avidity T cells were unaffected by low avidity T cells.

Conclusions:

Low avidity CD8 T cells do not hinder anti-tumor responses mediated by high avidity T cells.
These findings suggest low avidity T cells are not detrimental and are part of natural T cell responses.
This is a reassuring conclusion for understanding natural anti-tumor immunity.