Peripheral Blood as the Sole Source for Cancer Neoantigen and Reactive T-Cell Discovery.

Authors

Andrea Garcia-Garijo, Immaculada Creus-González, Pierre L Levy, Ana Belén Moreno-Cárdenas, Endika Prieto-Fernández, Maria Lozano-Rabella, Carlos Alberto Fajardo, Ricardo Pujol-Borrell, Albert Marín-Bayo, Johanna Kusnick, Jonatan Gonzalez, Carla Brujas, Jared J Gartner, Anna Yuste-Estevanez, Alma M Calahorro, Aya Louhamane, Jose Fernandez, Rebeca Sanz-Pamplona, Thomas B K Watkins, Vladimir Galvao, Eva Munoz-Couselo, Javier Ros, Elena Élez, Mafalda Oliveira, Cristina Saura Manich, Irene Brana, Ana Oaknin, Ramon Alemany, Josep Tabernero, Raquel Perez-Lopez, Simon Turcotte, Alexander M Frankell, Elena Garralda, Rodrigo A Toledo, Alena Gros

Published in

Cancer discovery. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

Neoantigen-targeted T-cell therapies require invasive tumor biopsies to identify neoantigens and reactive T cells, limiting their applicability and potentially underestimating tumor heterogeneity. We propose a novel strategy relying solely on peripheral blood to identify non-synonymous mutations via cell-free DNA whole-exome sequencing and isolate neoantigen-specific CD4+ and CD8+ T cells based on PD-1 and CD39 co-expression. Our method identified most neoantigens and increased the number of T-cell reactivities detected by standard biopsy-based techniques in an initial cohort of eight metastatic cancer patients. Critically, our approach uncovered additional neoantigens missed by tumor biopsy analysis, highlighting the potential for broader neoantigen targeting using liquid biopsies. Analysis of a cohort of 69 metastatic cancer patients revealed that approximately half could be eligible for our blood-only approach. This proof-of-concept study demonstrates the potential of using blood as a surrogate or complement for tumor biopsies to develop neoantigen-reactive T-cell therapies against a broader spectrum of neoantigens.

PMID:
42806482
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.