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Timnik, V.R.* ; Zoeschg, A.* ; Diederich, S.* ; Nefzger, S.M.* ; Huang, Z.* ; Schmid, N.A.* ; Giller, M.* ; Steiger, K.* ; Combs, S.E. ; Kroemer, G.* ; Schmid, T.E. ; Fischer, J.C.*

Experimental investigation of hematological toxicity after radiation therapy combined with immune checkpoint inhibitors.

Int. J. Radiat. Oncol. Biol. Phys. 123, 523-535 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
PURPOSE: Combining immune checkpoint inhibitors (ICIs) with radiation therapy (RT) has led to significant advancements in cancer treatment. However, evidence from clinical and experimental studies suggests that this combination may increase hematopoietic and lymphatic toxicity. This study aims to investigate the effects of the concurrent application of ICIs (anti-PD-1 and anti-CTLA-4) on radiation-induced hematopoietic and lymphatic injuries under standardized and controlled experimental conditions. MATERIALS AND METHODS: We utilized various experimental models in C57BL/6 and BALB/c mice to evaluate the impact of ICIs combined with RT on the hematopoietic system. These models involved different RT doses, regimens, and target sites in both healthy and tumor-bearing mice. RESULTS: Our findings showed that the concurrent use of ICIs did not meaningfully affect post-RT pancytopenia kinetics or the regeneration of specific blood cell lineages over time. Consistently, combining RT with ICIs did not significantly enhance DNA damage in immune cells within the bloodstream. This outcome was comparable across different RT doses, regimens, and target sites and was reproducible in both tumor-bearing and non-tumor-bearing mice. Additionally, there were no significant increases in late side effects, including reductions in bone marrow cell counts or megakaryocyte numbers, after combined radioimmunotherapy. CONCLUSION: These findings suggest that combining ICIs with RT does not exacerbate hematological toxicity. This information is valuable for interpreting adverse events in clinical trials involving radioimmunotherapy and for predicting potential hematological side effects in cancer patients receiving these treatments.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Anemia ; Bone Marrow ; Immune Checkpoint Inhibition ; Immune-related Adverse Events ; Leukopenia ; Megakaryocytes ; Neutropenia ; Radiation Therapy ; Thrombocytopenia; Bone-marrow; Irradiation; Radiotherapy; Anti-pd-1; Blockade; Mice
ISSN (print) / ISBN 0360-3016
e-ISSN 0360-3016
Zeitschrift International Journal of Radiation Oncology, Biology, Physics
Quellenangaben Band: 123, Heft: 2, Seiten: 523-535 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Medicine (IRM)