S2551
Radiobiology - Microenvironment
ESTRO 2026
fold increase in high-mannose glycan structures (ConA) and in sialylation (MAL II) following 2-20 Gy exposure (Fig. 1A). Correspondingly, qPCR revealed upregulation of sialyltransferases associated with MAL II–recognized structures (Fig. 1B). In parallel, RT also increased ICAM-1 expression (Fig. 1C), a key adhesion molecule mediating T-cell transmigration. Since high- mannose (ConA-reactive) glycosylation of ICAM-1 has previously been shown to enhance monocyte and neutrophil adhesion, our next step is to determine how RT-induced glycan remodeling, particularly of ICAM-1, affects T-cell adhesion and subsequent infiltration into the irradiated tumor microenvironment.
Cancer78, 1442–1448 (1998).3. Sinno, N. et al.Phys. Med. Biol.67, 245013 (2022).4. Lunt, S. J. et al.BMC Cancer8, 1–14 (2008).5. Milosevic, M. et al.Microvasc. Res.75, 381–390 (2008). Keywords: Pharmacokinetics, Imaging, Tumour microenvironment
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Enhancing T cell tumor infiltration via radiotherapy-controlled endothelial cell glycosylation Lenneke A.M. Cornelissen, Maaike W.G. Looman, Jan Bussink, Gosse J. Adema Radiation Oncology, Radboudumc, Nijmegen, Netherlands Purpose/Objective Radiotherapy (RT) not only exerts direct cytotoxic effects on tumor cells but also profoundly remodels the tumor microenvironment (TME), influencing immune cell recruitment and function. T-cells play a pivotal role in recognizing and eliminating cancer cells. However, despite the success of T-cell-based immunotherapies, clinical response rates remain below 30%, partly due to limited T-cell trafficking into tumors. Effective T-cell infiltration requires transmigrate across the tumor endothelium, a process that relies on the coordinated activity of adhesion molecules which activity depends on glycosylation. Glycosylation is biochemically linked with metabolic pathways, making it highly sensitive to metabolic disturbances. Notably, cellular metabolism is profoundly affected by RT, and emerging evidence indicates that RT can alter protein glycosylation, including endothelial cells glycosylation with functional consequence on monocyte adhesion. Building on these findings, this study aims to elucidate the mechanisms by which RT alters endothelial glycosylation to enhance T-cell adhesion and infiltration into the irradiated TME. Material/Methods Human endothelial cells lines, Human Microvascular Endothelial Cells (HMECs) [1, 2] and Human Aortic Endothelial cells (HAECs), were cultured and treated with 0,2,4, and 20 Gy single fraction X-rays. Glycosylation and adhesion molecules were measured at day 4 upon RT using (lectin) flow cytometry. Various types of lectins exist and each of them recognize a certain specific glycan structure expressed on the cell surface of the endothelial cells. Validation of changes in glycosylation was done by qPCR on key genes involved in glycosylation pathway. Results RT caused a dose-dependent alteration of endothelial glycosylation. Both HMECs and HAECs showed a 1.5–2-
Conclusion Our findings demonstrate that RT changes endothelial cell glycosylation, as well as enhanced expression of the adhesion molecule ICAM-1. These radiation-driven modifications suggest a coordinated remodeling of the endothelial surface that may directly influence immune cell interactions, highlighting novel opportunities to integrate RT with T-cell-based immunotherapy to improve anti-tumor immunity and patient outcomes. References [1] Ades EW, Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, Lawley TJ. HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol. 1992 Dec;99(6):683-90. doi: 10.1111/1523- 1747.ep12613748. PMID: 1361507. [2] Bouïs D, Hospers GA, Meijer C, Molema G, Mulder NH. Endothelium in vitro: a review of human vascular endothelial cell lines for blood vessel-related research. Angiogenesis. 2001;4(2):91-102. doi: 10.1023/a:1012259529167. PMID: 11806248.
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