ESTRO 2024 - Abstract Book

S5174

Radiobiology - Immuno-radiobiology

ESTRO 2024

References:

1 Sini C, Fiorino C, Perna L, et al. Dose–volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation. Radiotherapy and Oncology . 2016;118(1):79-84.

1472

Proffered Paper

GeoMX spatial transcriptomics of TDLN after chemoradiotherapy and ICI in T3-4N0-1 NSCLC patients

Sofie Koomen 1 , Ezgi B Ulas 2 , Anne Vrijmoet 3 , Chris Dickhoff 4 , Idris Bahce 2 , Suresh Senan 5 , Tanja D de Gruijl 6 , Marieke Fransen 2 , Teodora Radonic 3 , Febe van Maldegem 1 , Famke L. Schneiders 5 1 Amsterdam UMC, MCBI, Amsterdam, Netherlands. 2 Amsterdam UMC, Department of Pulmonary Medicine, Amsterdam, Netherlands. 3 Amsterdam UMC, Department of Pathology, Amsterdam, Netherlands. 4 Amsterdam UMC, Department of Thoracic Surgery, Amsterdam, Netherlands. 5 Amsterdam UMC, Department of Radiation Oncology, Amsterdam, Netherlands. 6 Amsterdam UMC, Department of Medical Oncology, Amsterdam, Netherlands

Purpose/Objective:

Tumor-draining lymph nodes (TDLN) play a key role in fostering the immunogenic response against tumors. A study was performed to evaluate neoadjuvant immune checkpoint-based immunotherapy with chemoradiotherapy (CRT) followed by surgical intervention, in patients with locally advanced non-small cell lung cancer (NSCLC). As TDLN are often situated in the proximity of the tumor, they are exposed to the effects of radiotherapy. However, the precise impact of these induction therapies on the immune-related functions of TDLN are poorly understood. We studied the immunomodulatory effects in TDLN of T3-4N0-1 NSCLC patients by using a combination of immunohistochemistry (IHC) analyses and spatial transcriptomics profiling via GeoMX technology.

Material/Methods:

Resected lymph nodes were collected from two distinct groups of patients. The first group consisted of patients (n=25) participating in the INCREASE trial [EudraCT-Number: 2019–003454-83; Netherlands Trial Register number: NL8435] who underwent a treatment regimen involving neoadjuvant ipilimumab/nivolumab combined with chemoradiotherapy (CRT) followed by surgical resection. The second group included a control cohort of NSCLC patients (n=25) matched to the first group, who received standard CRT induction therapy. The selection of lymph nodes was based on the dose of radiation received, categorized as low (<5 Gy), intermediate (20-30 Gy), or high dose (50-60 Gy). These lymph nodes were subjected to duplex immunohistochemistry, focusing on combinations of CD8/Ki67, PD1/FOXP3, and CD8/cleaved caspase-3, with specific analysis conducted on manually identified hotspot regions. Additionally, spatial transcriptomics profiling using GeoMX technology was carried out through a Technology Access Program. This involved DNA staining in conjunction with CD8, Ki67, and CD11a markers, and included UV-mediated release of oligos of Regions Of Interest (ROI), followed by oligo collection and sequencing.