Peripheral Blood as the Sole Source for Cancer Neoantigen and Reactive T-Cell Discovery
(1) Garcia-Garijo A (2) Creus-Gonzlez I (3) Levy PL (4) Moreno-Crdenas AB (5) Prieto-Fernndez E (6) Lozano-Rabella M (7) Fajardo CA (8) Pujol-Borrell R (9) Marn-Bayo A (10) Kusnick J (11) Gonzalez J (12) Brujas C (13) Gartner JJ (14) Yuste-Estevanez A (15) Calahorro AM (16) Louhamane A (17) Fernandez J (18) Sanz-Pamplona R (19) Watkins TBK (20) Galvao V (21) Munoz-Couselo E (22) Ros J (23) lez E (24) Oliveira M (25) Saura Manich C (26) Brana I (27) Oaknin A (28) Alemany R (29) Tabernero J (30) Perez-Lopez R (31) Turcotte S (32) Frankell AM (33) Garralda E (34) Toledo RA (35) Gros A
To expand the accessibility of neoantigen-based immunotherapy, Garcia-Garijo et al. integrated circulating tumor DNA (ctDNA) whole-exome sequencing (WES) to identify non-synonymous mutations (NSMs) with the isolation of neoantigen-specific T cells from circulating CD8+PD1hiCD38+ and CD4+PD1hi populations. In 8 patients with metastatic solid cancers, this strategy identified most lesion-derived NSMs (and additional neoantigens) enriched for clonal variants. In a cohort of 69 patients with metastatic solid cancers, neoantigen discovery based only on ctDNA seemed feasible in ~50% of patients (~85% of patients with colorectal cancer).
Contributed by Ute Burkhardt
(1) Garcia-Garijo A (2) Creus-Gonzlez I (3) Levy PL (4) Moreno-Crdenas AB (5) Prieto-Fernndez E (6) Lozano-Rabella M (7) Fajardo CA (8) Pujol-Borrell R (9) Marn-Bayo A (10) Kusnick J (11) Gonzalez J (12) Brujas C (13) Gartner JJ (14) Yuste-Estevanez A (15) Calahorro AM (16) Louhamane A (17) Fernandez J (18) Sanz-Pamplona R (19) Watkins TBK (20) Galvao V (21) Munoz-Couselo E (22) Ros J (23) lez E (24) Oliveira M (25) Saura Manich C (26) Brana I (27) Oaknin A (28) Alemany R (29) Tabernero J (30) Perez-Lopez R (31) Turcotte S (32) Frankell AM (33) Garralda E (34) Toledo RA (35) Gros A
To expand the accessibility of neoantigen-based immunotherapy, Garcia-Garijo et al. integrated circulating tumor DNA (ctDNA) whole-exome sequencing (WES) to identify non-synonymous mutations (NSMs) with the isolation of neoantigen-specific T cells from circulating CD8+PD1hiCD38+ and CD4+PD1hi populations. In 8 patients with metastatic solid cancers, this strategy identified most lesion-derived NSMs (and additional neoantigens) enriched for clonal variants. In a cohort of 69 patients with metastatic solid cancers, neoantigen discovery based only on ctDNA seemed feasible in ~50% of patients (~85% of patients with colorectal cancer).
Contributed by Ute Burkhardt
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.
Author Info:
(1) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (2) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://
ror.org/054xx3904 (3) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (4) Vall d'Hebron Institute of Oncology Spain. ROR: https://ror.org/054xx3904 (5) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (6) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (7) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (8) Universitat Autnoma de Barcelona Barcelona, Barcelona Spain. ROR: https://ror.org/052g8jq94 (9) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (10) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (11) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (12) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (13) National Institutes of Health United States. ROR: https://ror.org/01cwqze88 (14) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (15) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (16) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (17) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (18) Instituto de Investigacin Sanitaria Aragn Zaragoza Spain. ROR: https://ror.org/03njn4610 (19) Stanford University Stanford, CA United States. ROR: https://ror.org/00f54p054 (20) Vall d'Hebron Institute of Oncology Barcelona Spain. ROR: https://ror.org/054xx3904 (21) Vall d'Hebron Institute of Oncology barcelona, barcelona, spain Spain. ROR: https://ror.org/054xx3904 (22) Vall d'Hebron Institute of Oncology (VHIO) Barcelona Spain. (23) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (24) Vall d'Hebron Institute of Oncology Barcelona Spain. ROR: https://ror.org/054xx3904 (25) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (26) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (27) Vall d'Hebron Institute of Oncology Barcelona Spain. ROR: https://ror.org/054xx3904 (28) Institut d'Investigaci Biomdica de Bellvitge L'Hospitalet de Llobregat Spain. ROR: https://ror.org/0008xqs48 (29) Vall d'Hebron Institute of Oncology Barcelona Spain. ROR: https://ror.org/054xx3904 (30) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (31) Centre Hospitalier de l'Universit de Montral Montreal Canada. ROR: https://ror.org/0410a8y51 (32) The Francis Crick Institute London United Kingdom. ROR: https://ror.org/04tnbqb63 (33) Vall d'Hebron Institute of Oncology Barcelona Spain. ROR: https://ror.org/054xx3904 (34) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904 (35) Vall d'Hebron Institute of Oncology Barcelona, Barcelona Spain. ROR: https://ror.org/054xx3904
Citation: Cancer Discov 2026 Sep 29 Epub09/29/2026
