ESTRO 2024 - Abstract Book

S5201

Radiobiology - Microenvironment

ESTRO 2024

Purpose/Objective:

Immunosuppressive tumour microenvironment features, which act as a barrier to brisk CD8+ T cell infiltration, typically characterise tumours which are associated with poor outcome. Here, we aimed to identify novel therapeutic targets to improve radiotherapy in tumours with immunosuppressive microenvironments.

Material/Methods:

We used an integrated screening approach, and multiple murine models, including tumour organoids originally derived from villinCreER Apcfl/fl KrasG12D/+ Trp53fl/fl TrgfbrIfl/fl (AKPT) mice. Subcutaneously grown AKPT tumours display features resembling those of colorectal cancers associated with poor outcome; includingstromal rich regions and poor CD8+ T-cell infiltration.

Results:

In tumours with an immunosuppressive microenvironment, we find that the complement system is the first immune system pathway to be upregulated following irradiation. Targeting complement receptor C5aR1 improves radiotherapy, even in tumours displaying poor CD8+ T-cell infiltration. We also uncover that targeting C5aR1 results in increased radiation-induced cell death specifically in tumours but not normal tissues which instead appear to be protected by C5aR1 depletion.

Conclusion:

Collectively, these data reveal that targeting C5aR1 improves radiotherapy in tumours displaying immunosuppressive features and could be used to open the therapeutic window of radiotherapy.

Keywords: immune excluded tumours

765

Proffered Paper

Immuno-molecular modulation in pancreatic cancer following ablative stereotactic body radiotherapy.

Christelle Bouchart 1,2 , Oier Azurmendi Senar 2 , Julie Navez 3,2 , Laurine Verset 4 , Anaïs Boisson 5 , Matthieu Hein 6 , Nicky D’Haene 7 , Dirk Van Gestel 1 , Luigi Moretti 1 , Pieter Demetter 8 , Jean-Baptiste Bachet 9 , Karen Willard-Gallo 5 , Rémy Nicolle 10 , Tatjana Arsenijevic 2 , Jean-Luc Van Laethem 11,2 1 Institut Jules Bordet - H.U.B, Radiation-Oncology, Brussels, Belgium. 2 ULB, Laboratory of Experimental Gastroenterology, Brussels, Belgium. 3 Hopital Erasme - H.U.B., Hepato-biliary-pancreatic surgery, Brussels, Belgium. 4 Institut Jules Bordet - H.U.B, Pathology, Brussels, Belgium. 5 Institut Jules Bordet - H.U.B, Molecular Laboratory Unit, Brussels, Belgium. 6 ULB, Medicine Faculty, Brussels, Belgium. 7 Hopital Erasme - H.U.B., Pathology, Brussels, Belgium. 8 ULB, Pathology, Brussels, Belgium. 9 La Pitié-Salpêtrière Hospital, Gastroenterology and