ESTRO 2024 - Abstract Book

S5184

Radiobiology - Immuno-radiobiology

ESTRO 2024

Table : Relative biological effectiveness in terms of RBEgrowth (MOC1 and MOC2) and RBETE (MOC1) for protons with (+) or without (÷) anti-PDL1 and synergygrowth (MOC1 and MOC2) and synergyTE (MOC1) and when combining X- or proton irradiation with anti-PDL1 (±S.E., [95 % CI]).

MOC1

MOC2

Treatment Effect (TE)

growth

growth

1.07±0.21 [0.67, 1.48]

0.89±0.04 [0.80, 0.98]

1.15±0.12 [0.91, 1.40]

RBE (÷ anti-PDL1)

1.19±0.20 [0.79, 1.59]

0.93±0.06 [0.81, 1.05]

1.60±0.17 [1.24, 1.96]

RBE (+ anti-PDL1)

1.30±0.25 [0.81, 1.80]

1.22±0.08 [1.05, 1.38]

0.96±0.11 [0.73, 1.19]

Synergy – X-rays

1.44±0.24 [0.96, 1.92]

1.27±0.06 [1.16, 1.38]

1.33±0.13 [1.06, 1.60]

Synergy – protons

Conclusion:

We found synergistic effects from combining protons and immunotherapy in the less immunogenic MOC2 tumor, which was not evident for X-rays. It was not possible to detect a systemic effect, as all animals bearing MOC2 tumor developed metastases. This is consistent with the in vitro findings of high immunosuppressive signalling in the MOC 2 cells, which was even higher after proton irradiation. In the immunogenic MOC1 tumor model, anti PDL1 had an effect alone, confirming that the tumor was already immunogenic. In this tumor, a synergistic effect of anti-PDL1 and irradiation was seen for both protons and X-rays, and high tumor effect appeared to prevent the development of metastases. In summary, protons appear to be a better choice when combined with ICI, but our findings warrant further investigation into immunosuppressive mechanisms.

Keywords: Proton therapy, immune checkpoint inhibitor,

2427

Digital Poster

Immunological signatures from irradiated cancer-associated fibroblasts

Turid Hellevik 1 , Rodrigo Berzaghi 2 , Inigo Martinez 2

1 University Hospital North Norway, Radiation Oncology, Tromsø, Norway. 2 University of Tromsø, Clinical Medicine, Tromsø, Norway

Purpose/Objective:

Cancer-associated fibroblasts (CAFs) are abundant and influential elements of the tumor microenvironment (TME), giving support to tumor development in multiple ways. Among other mechanisms, CAFs are important regulators of the immunological processes occurring in tumors. However, CAF-mediated tumor immunomodulation in the context of radiotherapy (RT) remains poorly understood. In this study, we explore potential effects of ionizing radiation (IR) on CAF-derived immunoregulatory signals to the TME.

Material/Methods: