ESTRO 2024 - Abstract Book

S5216

Radiobiology - Microenvironment

ESTRO 2024

Kris Raaijmakers, Rens Peters, Vera Mekers, Anne Beerkens, Maud Beekmans, Gosse Adema, Jan Bussink, Johannes Kaanders, Marleen Ansems

Radboudumc, Radiation Oncology, Nijmegen, Netherlands

Purpose/Objective:

Head and neck squamous cell carcinomas (HNSCC) is the most prevalent type of head and neck cancer, originating from the mucosal epithelium of the oral cavity, hypopharynx and larynx. Despite aggressive therapy, HNSCC is associated with a 5-year survival rate of less than 50%. The tumor microenvironment of late-stage HNSCC consists up to 80% of cancer-associated fibroblasts (CAFs). CAFs represent a heterogeneous group of cells that is actively involved in both tumor immunomodulation and matrix organization and have been ascribed both pro tumorigenic and anti-tumorigenic properties. The majority of HNSCC patients is treated with radiotherapy. Notably, CAFs are particularly radioresistant, and are associated with the development of tumor radioresistance. Still, the exact effect of radiotherapy on CAFs in HNSCC remains elusive. In this study, we aim to characterize both the effect of radiotherapy on CAFs, as well as its possible consequences for the tumor microenvironment.

Material/Methods:

Primary HNSCC CAFs were isolated from resection material of multiple patients, cultured, and exposed to a single dose of ionizing radiation in the range of 0-18 Gy ex vivo. Phenotypic changes of CAFs upon irradiation were evaluated via several microscopic techniques. Functional consequences of radiation of CAFs on HNSCC cell lines and peripheral blood mononuclear cells (PBMCs) were determined by co-culturing these cells with CAFs, or with CAF conditioned medium.

Results:

We fist validated the identity of CAFs that were isolated from resection material of HNSCC patients (fig. 1A). We demonstrate that CAFs have a significant capability to survive irradiation (fig. 1B), but that irradiation does reduce CAF proliferation (fig. 1C). In agreement, we find that irradiation triggers CAF senescence (fig. 1D). Furthermore, we demonstrate that soluble factors secreted by primary human HNSCC CAFs increase HNSCC cell migration, but that this effect does not change upon irradiation (fig. 1E). Similarly, co-culturing of CAFs with peripheral blood mononuclear cells (PBMCs) shows that CAFs affect the secretion of cytokines by activated PBMCs independent of radiotherapy.