ArticleInternational journal of radiation oncology, biology, physics2025
Radiation-Induced Lymphopenia: In Silico Replications of Preclinical Studies Suggest Importance of Dose to Lymphoid Organs.
Article in International journal of radiation oncology, biology, physics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Particle Arc Therapy in Cancer Radiotherapy: A Scoping Review of Feasibility and Dosimetric Evidence.Cancers · 2026Review
- The microbiota-lymphocyte protective axis (MLPA): a novel paradigm for overcoming radiation-induced lymphopenia (RIL) and potentiating the efficacy of tumor immuno-combination therapy.Cancer immunology, immunotherapy : CII · 2026Review
- Lymphocyte Kinetics and Outcomes After Comprehensive Involved-Site Radiotherapy for Oligometastases.Cancers · 2026Article
- No Evidence for Depletion of Circulating Lymphocyte Populations in Primary Brain Tumor Patients Receiving Radiation Therapy Alone.International journal of radiation oncology, biology, physics · 2026Article
- Local FLASH radiation exhibits a double-edged effect on the mouse immune system.Radiation oncology (London, England) · 2026Article
- The Challenges Discovering the Mechanisms Underlying Radiation-Induced Lymphopenia From Clinical Data.International journal of radiation oncology, biology, physics · 2026Article
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Abstract
purposeTo develop a computational framework to investigate the implications of lymphocyte recirculation for understanding radiation-induced lymphopenia (RIL) and to compare model predictions with preclinical in vivo studies. METHODS AND MATERIALS: A whole-body compartmental model of lymphocyte migration in mice was developed, and unknown rate parameters were fitted to published experimental data. Using a stochastic representation of the model in combination with detailed mouse phantom meshes, implicit lymphocyte trajectories were computed. In parallel, a module was developed to reproduce small animal irradiation plans using either photon or proton beams. Combining these computational tools, we calculated the dose distribution of the recirculating lymphocyte pool in different irradiation scenarios and simulated the subsequent redistribution of viable lymphocytes. The relative importance of irradiation of secondary lymphoid organs (SLOs) versus the blood was investigated through in silico replications of 3 preclinical studies in which mice were locally irradiated.
resultsLymphocyte recirculation between the blood and SLOs attenuates lymphocyte depletion in 1 compartment by distributing the loss throughout the system. Because only a relatively small fraction (∼17% for mice) of the recirculating lymphocyte pool is in the blood at any given time, with most lymphocytes in the SLOs, the effect of SLO irradiation is greater than that of the blood. Predicted depletion trends correlated with those observed in preclinical studies but underestimated the degree of lymphopenia. The finding that proton beams can avert lymphopenia after whole-brain irradiation by sparing head and neck lymph nodes was reproduced.
conclusionsThe occurrence of RIL is associated with worse outcomes in patients with cancer but remains poorly understood. Therefore, a computational framework to replicate preclinical studies was developed to systematically investigate this phenomenon. Our simulations indicate that irradiation of SLOs contributes more to lymphocyte dose than blood irradiation. However, the expected cytotoxicity associated with the replicated preclinical studies could not fully account for the degree of lymphopenia observed.
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