OS03.5.A Characterization of the inflammatory tumor microenvironment composition in solid cancer patients with brain metastases after progression to immune checkpoint inhibitor therapy

Abstract Background Immunotherapy (IO) has changed the treatment landscape of metastatic cancer patients, however, resistance is frequent. We aimed to characterize inflammatory tumor microenvironment in brain metastases (BM) after IO gain a deeper understanding immunologic escape mechanisms. Material and Methods Solid patients who had BM resection progression (IO cohort) were retrospectively identified. analyzed tumor-infiltrating immune cell subsets (CD3, CD8, CD45RO, FOXP3) expression checkpoint molecules (PD-L1, PD-1, LAG-3) by immunohistochemistry. A control cohort tissue samples without prior served for comparison (no immunotherapy cohort, NIO). Results Twenty-eight (12/28, 42.9% females; 16/28, 57.1% males; median 61 years; 14/28, 50% lung cancer; 5/28, 17.9% melanoma; 4/28, 14.3% renal carcinoma; 1/28, 3.6% breast other entities) 57 NIO (28/57, 49.1% 29/57, 50.9% 58 35/57, 61.4% 9/57, 15.8% 4/57, 7.0% 3/57, 5.3% 6/57, 10.5% included. one (range 0-4) systemic therapy line IO. Median time from last application until was 5.6 months 0.2-49.8 months). Patients received number 7 1-56) applications (14/28, PD-1-targeting IO; 8/28, 28.6% PD-L1; 2/28, 7.1% CTLA4; CTLA4+PD-1; 3/28, 10.7% IO+chemotherapy). No statistically significant differences densities investigated TILs or PD-L1 between observed. showed higher compared (57.1 vs. 42.1%, Chi-square, p>0.05). Overall survival (OS) similar both cohorts, with OS 11.0 5.0-17.0) 5.5-16.5) cohort. Conclusion Our findings show an upregulation occurring absence overt changes microenvironment. Ongoing analyses this are investigating possible molecular driver analyzing DNA methylation profiles pre-and post-IO potentially insights on mechanisms patients.