ESTRO 2026 Congress Report, radiobiology track by Serge Candéias, Katalin Lumniczky, Anna Dubrovska

When ionising radiation hits people, whether in medicine or the environment, it may interact in complex, multilayered, and longitudinal ways with the immune system [1]. The outcome of these interactions can range from detrimental effects to immune stimulation, depending on the radiation dose, volume, and duration of exposure. Over the past decade, considerable efforts have been made to develop efficient and safe radioimmunotherapy combinations for clinical use [2]. In this newsletter, we would like to spotlight complementary topics on radioimmune interactions that were discussed in ESTRO 2026 sessions and at the 8th workshop of the Multidisciplinary European Low-Dose Initiative (MELODI).

MELODI, as the European platform investigating the biological effects of low-dose ionising radiation, identified the impact of low-dose irradiation on the immune system as a key priority in its strategic research agenda and organised the 8th MELODI workshop to discuss this topic. The workshop, which was held in Grenoble, France, on 28-29 April 2026, was structured in four sessions that were focused on the following topics: i) the effects of radiation on normal tissues, which included a session dedicated to presentations by young scientists; ii) the immunomodulatory effects of radiation during cancer treatment; iii) space and high-linear-energy-transfer (LET) radiation; and iv) senescence and ageing. As a follow-up of the workshop, a high-profile, comprehensive review is in preparation.

The studies on radioimmune interactions that were presented at ESTRO 2026 narrowed the gap between basic radiation biology and radiation oncology practice. The ESTRO 2026 talks highlighted the distinct immunomodulatory effects that are induced in normal tissues and tumours by different types, forms, and doses of radiation in preclinical translational settings, as well as their potential clinical implications. Here we offer a few highlights from the topics discussed during the MELODI workshop and at the ESTRO 2026 sessions.

Exposure to radiation has immunological consequences, as circulating immune cells are constantly in the radiation field, and the immune system responds to cell and tissue damage to restore tissue homeostasis and function. The immunological outcome of radiation exposure depends on the targeted tissue: tissue type, healthy or diseased (non-malignant or malignant), its pre-existing immune status, the person’s age and sex, and radiation parameters including dose, dose rate, volume, quality, and spatial homogeneity.

In healthy tissues, radiation damage can induce inflammation, which, if unresolved, becomes detrimental (impaired stem cell renewal/tissue regeneration, neurocognitive deficits, lung fibrosis). Radiation-induced senescence may also cause unresolved inflammation that can promote the development of pre-neoplastic cells. These senescent cells can be generated by both out-of-field and non-targeted (bystander) effects. Some of these effects can be modulated by the microbiota, which is itself impacted by radiation exposure. There is clinical evidence that immunostimulation by low-dose intestinal irradiation is mediated by gut-microbiota-dependent systemic metabolic reprogramming. Bacterial species differentially affect the anticancer efficacy of radiotherapy in combination with anti-programmed-death-ligand 1 (anti-PD-L1) immunotherapy, because they regulate dendritic cell migration to tumour-draining lymph nodes. These findings highlight the importance of gut microflora analysis before treatment starts [3]. Immune activation can also be boosted by manipulating lipid metabolism and/or mitophagy in cancer cells.

In addition to radiation quality (photons vs. protons/carbon ions), dose delivery is important in order to maximise anti-tumour effects and minimise side effects. For example, spatially fractionated radiation therapy (SFRT) techniques have shown a better therapeutic ratio in radiotherapy of complex, bulky tumours compared with conventional radiation due to the significant increase they cause in levels of cytokines such as tumour necrosis factor ɑ (TNFɑ) and tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL), which mediate the bystander effect. SFRT also induces inflammation and immunomodulatory effects caused by releasing neoantigens and pro-inflammatory cytokines. Also, SFRT reprograms the tumour microenvironment and improve the antigen presentation and abscopal effect to the non-irradiated tumour sites [4]. Combining radiation therapy with immunotherapies might modulate immune activation [5] and optimise the contribution of the immune system to the treatment of solid tumours [6].

Exposure of non-malignant, inflamed tissues to low-dose radiation can reduce inflammation and alleviate associated pathological symptoms (inflammatory osteoimmunological syndromes and atherosclerosis development; this effect has been observed in mice that lack the apolipoprotein E gene). In these settings, non-linear effects are often observed; macrophages and neutrophils are thought to play key roles in this immunomodulation.

In preclinical models and patients, irradiation has strong effects on the homeostasis of circulating immune cells. Each immune cell lineage is affected differently; lymph node sparing alleviates this leucopenia. In clinics, radiation-induced lymphopenia (RIL) affects a significant proportion of patients and impacts their survival. RIL can be directly induced by radiation or even indirectly by, e.g., radiation-induced myeloid-derived suppressor cells. Integration of lymphocyte dose information with bone marrow, thymic and lymph node considerations is important to provide a comprehensive assessment of immune impairment that is induced by the treatment, and clinically translatable models have been proposed to better predict the risk of RIL [7].

 

These two meetings concluded that the radioimmune interaction was not limited to effects within the treatment field or to out-of-field low-dose exposure; it also had a systemic character, as depicted in Figure 1. The mechanistic interplay between radiotherapy and the immune system is complex and, for now, incompletely understood. This interaction depends on multiple factors including radiation (LET, total dose, rate, fractionation, spatial heterogeneity), the doses received by the immune system’s organs-at-risk (circulating lymphocytes, bone marrow and thymus), and immune system anatomy (such as tumour or tumour-draining lymph nodes). Clinical studies are underway to explore the safety and effectiveness of innovative radioimmunotherapy combinations and to make immune system preservation a clinically adopted treatment-optimisation strategy.

 

Figure 1. Overview of systemic effects of radiotherapy on the immune system. Created by the authors using OpenAI’s ChatGPT (12.07.2026; version GPT-5.6).

 

Dr Serge Candéias

University Grenoble Alpes

French Atomic Energy Commission (CEA) and

the French National Centre for Scientific Research (CNRS)

Grenoble, France

 

Dr Katalin Lumniczky

Department of Radiobiology and Radiohygiene

National Centre for Public Health and Pharmacy

Budapest, Hungary

 

Professor Anna Dubrovska
OncoRay – National Centre for Radiation Research in Oncology
Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology
Germany