REVIEW article
Front. Oncol.
Sec. Cancer Genetics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1625212
This article is part of the Research TopicAdvancements and Challenges in Blood-Based Biomarkers for Cancer ImmunotherapyView all articles
The prognostic and predictive value of peripheral immune-related proteins in patients with lung cancer treated with radiotherapy
Provisionally accepted
Shaowen Lyu1
Rianne D.W. Vaes1*
Francesco Cortiula1,2
Lizza E.L. Hendriks3
Marc A. Vooijs1
Dirk De Ruysscher1- 1Department of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands
- 2Department of Medical Oncology, University Hospital of Udine, Udine, Italy
- 3Department of Respiratory Medicine, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, Netherlands
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Lung cancer is the leading cause of cancer-related death world-wide. Although the standard of care for patients with advanced stage lung cancer has significantly improved with the advent of immunotherapy and targeted agents, the overall prognosis remains poor. It highlights the need for improved patient selection utilizing prognostic and predictive biomarkers. Given the limited feasibility of serial lung tumor tissue biopsies, liquid biopsies have gained specific interest in achieving this aim. Radiotherapy (RT), commonly used alongside systemic treatments, can induce the release of immuno-stimulatory and immuno-suppressive molecules, triggering immune- and inflammatory responses are triggered and associated molecules are released. This review specifically focusses on immune-related molecules that are measurable in the blood and which have potential prognostic and/or predictive value in patients with lung cancer treated with RT alone or in combination with systemic agents. Such immune-related molecules include cytokines and chemokines, soluble receptors and ligands, and molecules expressed on the immune cell surface of circulating immune cells. Classical cytokines IL-6, IL-8, and TGF-β1 were the most studied molecules in patients with lung cancer treated with RT and were associated with poor survival and increased risk of radiation-induced toxicity. To date, there are still some barriers before these promising findings can be implemented in regular clinical practice. Practical points to achieve this goal are also addressed in this review.
Keywords: lung cancer, Radiotherapy, biomarkers, prognostic, predictive, Peripheral Blood, immunerelated proteins
Received: 08 May 2025; Accepted: 17 Jun 2025.
Copyright: © 2025 Lyu, Vaes, Cortiula, Hendriks, Vooijs and De Ruysscher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rianne D.W. Vaes, Department of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.