A blood-based approach could enable personalized immunotherapy without the need for a tumor biopsy

by American Association for Cancer Research

edited by Sadie Harley, reviewed by Robert Egan

Sadie Harley

Scientific Editor

Meet our editorial team
Behind our editorial process

Robert Egan

Senior Editor

Meet our editorial team
Behind our editorial process Editors' notes

This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

peer-reviewed publication

trusted source

proofread

The GIST Add as preferred source

In a study published in Cancer Discovery, cancer neoantigens and neoantigen-specific T cells were identified from patient blood samples by analyzing circulating tumor DNA (ctDNA) and immune cells.

Alena Gros, Ph.D., is the senior author of the study and group leader of the Tumor Immunology and Immunotherapy Group at the Vall d'Hebron Institute of Oncology (VHIO) in Spain. Andrea Garcia-Garijo, Ph.D., is a postdoctoral fellow in Gros' group and first author of the study.

"Neoantigens, which are proteins produced by cancer cells, make tumors easily recognizable to the immune system, prompting it to mount an immune response against the cancer cells expressing these neoantigens," said Gros.

Because neoantigens are not found on normal cells, targeting them may be an effective and safe strategy for cancer immunotherapy, Gros explained. She noted that researchers are developing personalized immunotherapies that target neoantigens, including cancer vaccines and T cell-based therapies.

Finding targets without a biopsy

A crucial step in developing personalized immunotherapies is identifying the neoantigens and neoantigen-specific T cells present within each patient's tumor. Doing so can also help identify patients likely to benefit from immunotherapy, since the presence of these biomarkers indicates that a tumor may be immunogenic, she added.

"Currently, clinicians identify neoantigens and neoantigen-specific T cells by analyzing tumor tissue collected through a biopsy or other surgical procedure. However, many patients do not have easily accessible tumors or are not healthy enough to undergo an invasive biopsy or surgery," said Andrea Garcia-Garijo, Ph.D., a postdoctoral fellow in Gros' group and the study's first author.

As a less invasive alternative, Gros and colleagues examined whether they could identify neoantigens and neoantigen-specific T cells using only patient blood. They reasoned that the DNA shed by cancer cells into the bloodstream, known as ctDNA, could provide insights into the mutations present within a tumor.

Blood reveals targets across tumor lesions

The researchers isolated and sequenced ctDNA from blood samples of six patients with metastatic melanoma, breast cancer, head and neck cancer or colorectal cancer. They were unable to isolate ctDNA from the blood of two additional patients, one with breast cancer and the other with head and neck cancer. Gros explained that this is consistent with the fact that some tumors shed very little DNA.

Gros and colleagues analyzed the ctDNA sequences to identify neoantigens and compared the results with those obtained from conventional tumor tissue analysis of the same six patients. Across all six, ctDNA analysis identified 63.25% to 97.4% of the neoantigens identified by standard tumor tissue analysis.

CtDNA analysis also identified many neoantigens not found by standard tumor tissue analysis. The ability to detect neoantigens that could not be found in resected tumor tissue suggests that a blood-based approach may provide a more representative view of the different neoantigens found in patients with metastatic disease, Gros explained.

"Patients with advanced disease have tumors in different organs, so a biopsy of one tumor may not capture the neoantigens found in other lesions," she said.

"By accessing the blood, we can identify neoantigens present across different tumor lesions, as well as T cells able to recognize them. This gives us a broader picture of the cancer throughout the body and could help us develop T-cell therapies that target multiple tumor lesions, making it harder for the cancer to escape treatment."

The researchers also found that T cells isolated from the blood samples of six of eight patients recognized and reacted to neoantigens identified by ctDNA, tumor tissue or both.

Detection varies across cancer types

To evaluate the applicability of ctDNA for neoantigen discovery in a broader population, Gros and colleagues expanded their analysis to a separate cohort of 69 patients with various types of metastatic solid tumors. They found that ctDNA was detectable in 32 of 69 patients (46.4%) across solid tumor types, suggesting that a blood-based approach to neoantigen discovery may be possible in roughly half of patients.

Among 17 patients with colorectal cancer, ctDNA was detectable in 14 (82.4%), including patients with mismatch repair-deficient tumors, which typically express more neoantigens and are often treated with immunotherapies that target neoantigens.

Clinical promise needs broader validation

"Our study suggests that blood-based neoantigen identification has the potential to replace or complement the traditional tissue-based approach in many patients and cancer types," said Gros. "Because blood is easier and faster to collect than tumor tissue, this approach could reach patients who have inaccessible tumors or are unable to undergo a biopsy. It could also allow patients to begin treatment sooner because they wouldn't have to wait for a biopsy."

Gros also pointed to the potential of using the blood-based approach to examine how neoantigens and patient immune responses change during treatment, which could help clinicians monitor treatment responses and provide insights into tumor evolution and treatment resistance.

Limitations of the study include the small patient population and the low prevalence of certain cancer types within it. Gros noted that additional validation in larger patient cohorts is needed before the approach could be widely used in the clinic.

Publication details

Peripheral Blood as the Sole Source for Cancer Neoantigen and reactive T cell discovery, Cancer Discovery (2026). DOI: 10.1158/2159-8290.CD-25-1779

Journal information: Cancer Discovery

Clinical categories

OncologyAllergy and immunology Provided by American Association for Cancer Research Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

Citation: A blood-based approach could enable personalized immunotherapy without the need for a tumor biopsy (2026, September 29) retrieved 29 September 2026 from https://medicalxpress.com/news/2026-09-blood-based-approach-enable-personalized.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.