Sex-specific differences in abscopal responses to combined radiotherapy and immune checkpoint inhibition–insights from a multicenter study

Trommer M, Rühle A, Ehret F, Lamrani A, Schmitter C, Kaufmann J, Mäurer M, Wurschi G, Jiang P, Baehr A, Hardt A, Bodensohn R, Käsmann L, Waltenberger M, Gkika E, Scafa D, Layer JP, Troost EG, Elkhamisy SA, Jazmati D, Popp I, Neppl S, Hagemeier A, Besserer A, Ferdinandus S (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 16

Article Number: 1699362

DOI: 10.3389/fimmu.2025.1699362

Abstract

Purpose: Abscopal effects (AbE) during combined radiotherapy (RT) and immune checkpoint inhibition (ICI) represent a potential mechanism for systemic tumor control, yet sex-specific differences in these responses remain largely unexplored. We investigated sex-associated signals in outcomes of combined RT-ICI in a multicenter cohort. We analyzed the incidence of AbE and survival outcomes with respect to clinical and biomedical markers. Methods: In this observational multicenter study, patients with metastatic solid tumors receiving RT-ICI and showing at least one non-irradiated lesion (NIL), assessed using iRECIST criteria, were analyzed. Abscopal response (AR) was defined as ≥30% reduction in NIL size, abscopal progression (AP) as ≥20% increase, and abscopal control (AC) as changes within this range. Results: Among 3,773 screened patients, 142 met the inclusion criteria (62% male, median age 62 years; 38% female, median age 58 years). AR and AC occurred more frequently in females (24% vs. 14%, 35% vs. 31%). While OS showed no significant difference (p=0.81), Cox regression analyses revealed significant associations of a longer ICI-to-RT-interval (males: HR = 0.903 [0.833–0.978], p=0.012; females: HR = 0.748 [0.621–0.900], p=0.002) and a BMI ≥25 kg/m² with survival in both sexes (males: HR = 4.282 [1.473–12.446], p=0.008; females: HR = 4.801 [1.182–19.502], p=0.028 with survival in both sexes). Elevated C-reactive protein (CRP) (≥5 mg/L) showed prognostic significance only in males (HR = 4.764 [1.184–19.170], p=0.028). Conclusion: Our findings suggest the possibility of sex-specific patterns in AbE occurrence. Additionally, our analyses identified sex-associated prognostic factors, including the importance of ICI-to-RT interval and BMI in both sexes and the male-specific prognostic value of CRP. These observations warrant further research and consideration in designing personalized RT-ICI combination strategies.

Authors with CRIS profile

Allison Lamrani Department of Radiation Oncology Charlotte Frei Department of Radiation Oncology

Involved external institutions

Klinikum der Universität München (LMU Klinikum) DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Köln DE Germany (DE) Klinikum Ernst von Bergmann DE Germany (DE) Universitätsklinikum Jena DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Nationales Centrum für Tumorerkrankungen (NCT) DE Germany (DE) Universitätsklinikum Düsseldorf DE Germany (DE) Universität Leipzig DE Germany (DE)

How to cite

APA:

Trommer, M., Rühle, A., Ehret, F., Lamrani, A., Schmitter, C., Kaufmann, J.,... Ferdinandus, S. (2026). Sex-specific differences in abscopal responses to combined radiotherapy and immune checkpoint inhibition–insights from a multicenter study. Frontiers in Immunology, 16. https://doi.org/10.3389/fimmu.2025.1699362

MLA:

Trommer, Maike, et al. "Sex-specific differences in abscopal responses to combined radiotherapy and immune checkpoint inhibition–insights from a multicenter study." Frontiers in Immunology 16 (2026).

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