S2529
Radiobiology – Immuno-radiobiology
ESTRO 2026
numbers, effector function, and reduced exhaustion of CD4 ⁺ and tumor-specific CD8 ⁺ TILs, along with elevated CD80 ⁺ CD86 ⁺ DCs in abscopal tumors (n=6- 9, p<0,05), as shown by flow cytometry. CD4 ⁺ T cell depletion during RT/ α PD-1/ α CTLA-4 treatment compromised control of the abscopal (n=6-13, p<0,05), but not irradiated tumors, leading to reduced infiltration of tumor-specific CD8 ⁺ T cells (n=6, p<0,05), along with impaired conventional DC1-mediated cross- presentation (n=6-7, p<0,05) in abscopal tumors. Mechanistically, activated CD4 ⁺ T cells promoted CD80/CD86 expression on cDC1s and enhanced tumor antigen cross-presentation to CD8+ T cells, partly via IFN- γ and TNF. Conclusion: hRT/ ⍺ PD-1/ ⍺ CTLA-4 triple treatment induced more cytotoxic effector TILs than hRT/ ⍺ PD-1/IL-2c treatment. Moreover, our results suggest that CD4+ effector T cells contribute to tumor control at abscopal sites by enhancing DC-mediated cross-presentation of tumor antigens to CD8+ T cells originating from the irradiated tumor. Keywords: Abscopal effect, immunotherapy, CD4+ T cells Dual immune checkpoint inhibition sensitizes low- immunogenic orthotopic rectal cancer subtypes to radioimmunotherapy Nicole A. Schmid 1 , Sarah Diederich 1 , Maximilian Giller 1 , Sophie M. Nefzger 1 , Stephanie E. Combs 1,2 , Markus Tschurtschenthaler 2,3 , Julius C. Fischer 1 1 Department of Radiation Oncology, Klinikum rechts der Isar, TUM-School of Medicine and Health, Technical University of Munich, Munich, Germany. 2 German Cancer Consortium (DKTK), Partner-site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany. 3 Technical University of Munich, TUM School of Medicine and Health, Center for Translational Cancer Research (TranslaTUM), Munich, Germany Purpose/Objective: A key prognostic marker in colorectal cancer patients is the degree of immune infiltration into tumor tissue. Patients can thereby be grouped into having hot tumors or cold tumors. Hot tumors are characterized by a high number of CD8+ T-cells infiltrating the tumor Mini-Oral 2191 microenvironment (TME). These patients respond more frequently to immune checkpoint inhibition (ICI). In contrast, ICI has limited effects on cold tumors, which are characterized by low scores of T-cell infiltration. The majority of rectal cancer patients belong to the latter group and display only limited CD8 ⁺ T-cells within the TME. A central question in this
considered for the delivery of heterogeneous fractionation schemes, particularly when combined with immunotherapy. Keywords: Fractionated Radiotherapy, Radioimmunotherapy Proffered Paper 2126 Immunoradiotherapy-induced CD4+ T cells enhance abscopal responses by promoting antigen cross-presentation Xi Rao 1,2 , Kateryna Onyshchenko 3 , Ting Li 1 , Meidan Wang 1 , Simone Gaedicke 1 , Anca-Ligia Grosu 1,2 , Elke Firat 1 , Gabriele Niedermann 1,2 1 Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 2 German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany. 3 Department of Urology, Emory University School of Medicine, Atlanta, USA Purpose/Objective: The local effect of radiotherapy (RT) is enhanced by CD8 ⁺ T cell responses elicited through dendritic cell (DC)-mediated cross-presentation of tumor antigens, facilitated by RT-induced damage-associated molecular patterns (DAMPs). The abscopal effect – regression of non-irradiated tumors – has been observed clinically, particularly in combination with immune checkpoint blockade, although it remains uncommon. To better understand how to enhance this effect, we investigated two RT/ α PD-1-based triple combinations incorporating either α CTLA-4 or CD122- targeted IL-2 complexes (IL-2c). Material/Methods: In mice bearing bilateral subcutaneous C51 colon carcinoma or B16 melanoma tumors, the primary tumor received local irradiation with two fractions of either 8 Gy or 12Gy. Treatment with ⍺ PD1 and ⍺ CTLA4 was given concurrently with RT and weekly thereafter; IL2c was injected intraperitoneally for 3 consecutive days. In addition to monitoring tumor growth and survival, tumor-specific CD8+ T cells were determined flow cytometrically using MHC-I tetramers and various antibodies. Furthermore, the effector functions of CD8+ and CD4+ TILs and tumor antigen cross- presentation by DCs were evaluated. Results: In the C51 model, RT/ α PD-1/ α CTLA-4 induced a stronger abscopal effect than RT/ α PD-1/IL- 2c, hRT+ ⍺ PD-1 and hRT+ ⍺ CTLA-4 (8-13 mice per group, p<0,05), respectively. RT/ α PD-1/ α CTLA-4 achieved a 61.5% abscopal cure rate, dependent on both CD8 ⁺ and CD4 ⁺ T cells. In contrast, the less effective RT/ α PD-1/IL-2c response required only CD8 ⁺ T cells. The enhanced abscopal effect with RT/ α PD-1/ α CTLA-4 was associated with increased
Made with FlippingBook - Share PDF online