Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors

Julien Schmidt, Johanna Chiffelle, Marta A. S. Perez, Morgane Magnin, Sara Bobisse, Marion Arnaud, Raphael Genolet, Julien Cesbron, David Barras, Blanca Navarro Rodrigo, Fabrizio Benedetti, Alexandra Michel, Lise Queiroz, Petra Baumgaertner, Philippe Guillaume, Michael Hebeisen, Olivier Michielin, Tu Nguyen-Ngoc, Florian Huber, Melita Irving, Stéphanie Tissot-Renaud, Brian J. Stevenson, Sylvie Rusakiewicz, Denarda Dangaj Laniti, Michal Bassani-Sternberg, Nathalie Rufer, David Gfeller, Lana E. Kandalaft, Daniel E. Speiser, Vincent Zoete, George Coukos and Alexandre Harari ()
Additional contact information
Julien Schmidt: Agora Cancer Research Center
Johanna Chiffelle: Agora Cancer Research Center
Marta A. S. Perez: Agora Cancer Research Center
Morgane Magnin: Agora Cancer Research Center
Sara Bobisse: Agora Cancer Research Center
Marion Arnaud: Agora Cancer Research Center
Raphael Genolet: Agora Cancer Research Center
Julien Cesbron: Agora Cancer Research Center
David Barras: Agora Cancer Research Center
Blanca Navarro Rodrigo: Agora Cancer Research Center
Fabrizio Benedetti: Agora Cancer Research Center
Alexandra Michel: Agora Cancer Research Center
Lise Queiroz: Agora Cancer Research Center
Petra Baumgaertner: Agora Cancer Research Center
Philippe Guillaume: Agora Cancer Research Center
Michael Hebeisen: Agora Cancer Research Center
Olivier Michielin: Lausanne University Hospital
Tu Nguyen-Ngoc: Agora Cancer Research Center
Florian Huber: Agora Cancer Research Center
Melita Irving: Agora Cancer Research Center
Stéphanie Tissot-Renaud: Agora Cancer Research Center
Brian J. Stevenson: Agora Cancer Research Center
Sylvie Rusakiewicz: Agora Cancer Research Center
Denarda Dangaj Laniti: Agora Cancer Research Center
Michal Bassani-Sternberg: Agora Cancer Research Center
Nathalie Rufer: Agora Cancer Research Center
David Gfeller: Agora Cancer Research Center
Lana E. Kandalaft: Agora Cancer Research Center
Daniel E. Speiser: Agora Cancer Research Center
Vincent Zoete: Agora Cancer Research Center
George Coukos: Agora Cancer Research Center
Alexandre Harari: Agora Cancer Research Center

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract The success of cancer immunotherapy depends in part on the strength of antigen recognition by T cells. Here, we characterize the T cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities of 371 CD8 T cell clones specific for neoantigens, tumor-associated antigens (TAAs) or viral antigens isolated from tumors or blood of patients and healthy donors. T cells from tumors exhibit stronger functional and structural avidity than their blood counterparts. Relative to TAA, neoantigen-specific T cells are of higher structural avidity and, consistently, are preferentially detected in tumors. Effective tumor infiltration in mice models is associated with high structural avidity and CXCR3 expression. Based on TCR biophysicochemical properties, we derive and apply an in silico model predicting TCR structural avidity and validate the enrichment in high avidity T cells in patients’ tumors. These observations indicate a direct relationship between neoantigen recognition, T cell functionality and tumor infiltration. These results delineate a rational approach to identify potent T cells for personalized cancer immunotherapy.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38946-z

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DOI: 10.1038/s41467-023-38946-z

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