ESTRO 2025 - Abstract Book

S3879

Radiobiology - Immuno-radiobiology

ESTRO 2025

Keywords: DNA damage response, IFN, high-LET radiation

2359

Poster Discussion Differences in immune cell subtypes in peripheral blood lymphocytes during the complex therapy of triple negative breast cancer patients Zsuzsa S Kocsis 1,2 , Gyöngyvér Orsolya Sándor 1,2 , Gyöngyi Farkas 1 , Gábor Székely 1 , Gábor Rubovszky 3,2 , Borbála Székely 3,2 , Ákos Sávolt 4 , Viktor Smanykó 5 , Zoltán Takácsi-Nagy 5,2,6 , Csaba Polgár 5,2,6 , Zsolt Jurányi 1,2 1 Department of Radiobiology and Diagnostic Onco-Cytogenetics, Centre of Radiotherapy, National Institute of Oncology, Budapest, Hungary. 2 National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary. 3 Department of Clinical Pharmacology, Chest and Abdominal Tumours Chemotherapy "B", National Institute of Oncology, Budapest, Hungary. 4 Department of Breast and Sarcoma Surgery, National Institute of Oncology, Budapest, Hungary. 5 Centre of Radiotherapy, National Institute of Oncology, Budapest, Hungary. 6 Department of Oncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary Purpose/Objective: In triple negative breast cancer immunotherapies are increasingly applied due to poor prognosis. PD1/PDL1 immunohistochemical staining data are not specific enough to predict the effectiveness of checkpoint inhibitor blockade therapies. If we knew how chemotherapy, surgery and radiotherapy affect the number of the immune cell subpopulations, which exert the effect, more effective combination schedules could be designed. Material/Methods: We recruited 167 triple negative breast cancer patients, who received systemic treatments, undergone surgery and radiotherapy, second chemotherapy and anti-PD1 therapy if indicated. We took blood at baseline, after every modality and three months after completion of the complex treatment. Subpopulations of NK cells, cytotoxic T cells and regulatory T cells were analyzed. Results: We measured cc. 700 samples of 27 patients with no immunotherapy and 11 healthy controls. We found that CD8+ PD1+ cell occurrence was significantly higher in patients (baseline) than in controls (3.7±2.3% vs. 1.8±2.3%, p=0.021) and no significant decrease due to therapies was seen. TIM3+ (3.9±3.4% vs. 8.6±5.7%, p=0.0001), ICOS+ (0.9±1.0% vs. 2.9±3.7%, p=0.043), VISTA+ (16.3±19.9% vs. 18.5±5.9%, p=0.023) and TIGIT+ (23.0±20.3% vs. 45.6±15.2%, p=0.011) CD8+ cells and PD1+ NK cells (4.3±7.7% vs. 28.3±10.1% p<0.001) were decreased in patients before therapy vs. controls. Although after chemo- and radiotherapy increased number of these cells (except TIGIT+ cells) was seen, it was not significant and three months after the complex therapy there were still significant differences between patients and controls. However, Granzym B+ (50.9±16.9% vs. 31.4±16.7%, p=0.005), perforin+ (49.3±14.5% vs. 31.0±18.2%, p=0.006) and CD3 zeta+ NK cells (50.9±16.9% vs. 31.4±16.7%, p=0.049) were less frequent in the baseline patients than in the controls, but three months after the complex therapy, there were no significant differences anymore. We compared values in the patients with (n=12) and without (n=10) pathological complete remission (pCR) after neoadjuvant chemotherapy. We found significantly more perforin+ FoxP3+ cells (7.5±8.5% vs. 34.6±37.2% p=0.039) in patients with pCR. There were also differences in degranulating NK cells (14.3±4.5% % in pCR and 11.9±6.9% in no pCR, p=0.065) and TIM3+CD8+ (2.8±1.8% in pCR and 5.6±4.7% in no pCR, p=0.081). Conclusion: According to differences between pCR and non-pCR patients, predictive markers might be developed for optimal treatment selection. After further investigation, our results on cell population changes can show us what sequence of modalities will be more beneficial in combination with immunotherapy. Keywords: immunotherapy marker, radio-immunology, biomarker