ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026
Modulation of HMGB1, PRF1, TRAIL, and M-CSF after TARGIT-IORT in breast-conserving surgery: defining a unique acute immune landscape.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundTargeted intraoperative radiotherapy (TARGIT-IORT) delivers a single high-dose boost to the tumor bed during breast-conserving surgery (BCS) and is now recommended only within clinical trials or registries. Its acute systemic immunogenic effects relative to BCS-only are not well characterized.
methodsWomen with histologically confirmed breast carcinoma were allocated in an alternating 1:1 sequence to BCS + TARGIT-IORT or BCS-only groups. Peripheral blood was sampled pre-operatively and 24 h post-surgery. ICD and cytokine/DAMP mediators, including HMGB1, PRF1, TRAIL, FASL-NFSF6, CASP-8, GZMB, CRT, TLR4, RAGE, GDF15, and M-CSF, were quantified using ELISA. Perioperative changes were analyzed using the Wilcoxon signed-rank test; between-group Δ differences were assessed using the Mann-Whitney U test.
resultsForty-two patients were enrolled (26 BCS + TARGIT-IORT; 16 BCS-only). TARGIT-IORT induced a distinct early immune shift across ICD markers. HMGB1 showed the most pronounced change (3410.5 → 359.8 pg/ml; p < 0.001), significantly greater than that after BCS-only (1040.7 → 263.6 pg/ml; Δp < 0.001). TRAIL (246.1 → 155.5 pg/ml; p = 0.001) and FASL-NFSF6 (1087.1 → 839.3 pg/ml; p = 0.003) also declined significantly after TARGIT-IORT, whereas changes following BCS alone were modest. TARGIT-IORT increased M-CSF (266.7 → 386.7 pg/ml; p = 0.037) and reduced TLR4 (1456.3 → 1331.3 ng/ml; p = 0.007), with no significant perioperative changes in RAGE, GDF15, CRT, GZMB, or CASP-8. DISCUSSION: Within 24 h, TARGIT-IORT generates a coordinated ICD-related and cytokine/DAMP signature, marked HMGB1 depletion, death ligand modulation, TLR4 engagement, and M-CSF upregulation, consistent with rapid immune priming. These findings are exploratory and should be interpreted within a translational framework. Larger, randomized multicentre studies with extended longitudinal and tissue-level immune profiling are needed to confirm these signals.
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