Radiation-induced changes in the inflammatory microenvironment composition of lung cancer brain metastases.

Abstract

2528 Background: Radiotherapy was postulated to impact the inflammatory microenvironment composition in patients with lung cancer brain metastases (BM). Methods: Formalin fixed and paraffin embedded BM specimens from treatment naïve patients (group 1) and from patients treated with radiation therapy including whole brain radiotherapy and/or stereotactic radiosurgery (group 2) or prophylactic cranial irradiation (group 3) before BM resection were identified from the Vienna Brain Metastasis Registry. T cell subsets (CD3+,CD8+,CD45RO+,FOXP3+,PD-L1+) were investigated using the Ventana Benchmark Ultra system Definiens software. Results: Specimens from 41 patients (28/41;68.3% NSCLC, 13/41;31.7% SCLC) were included in the study. A significant difference in CD3+TIL density between group 1 (median: 964.5cells/mm2) and group 2 (median: 283.4cells/mm2; p-value=0.021; Mann-Whitney-U test), as well as group 3 (median: 168.8 cells/mm2; p-value= 0.028; Mann-Whitney-U test) were observed. Furthermore, CD8+ and FOXP3+TIL densities of group 2 (CD8+ median: 172.1cells/mm2; FOXP3+ median: 210.7cells/mm2) were numerically lower compared to group 1 (CD8+ median: 190.1 cells/mm2; FOXP3+ median: 221.2 cells/mm2). Of 10/41 (24.4%) patients further resected BM tissue specimens after initial resection were available. Here, the inflammatory microenvironment of BM treated with radiation therapy between the resections was significantly associated with lower densities of CD3+ (median: 105.1 cells/mm2) and CD8+ (median: 20.3cells/mm2) compared to radiation-naïve patients (CD3+ median: 825.4cells/mm2; CD8+median: 105.5cells/mm2; p=0.037; Mann-Whitney U-test). Conclusions: Radiation treatment was associated with lower densities of TIL subsets in our BM cohort. Although results have to be interpreted with caution due to the limited sample size, further studies investigating the sequencing of radiotherapy and immune modulating therapies might be of interest. [Table: see text]