Abstract 369P
Background
Immunotherapy (IO) is an important pillar in the treatment of various advanced solid cancers, but resistance is frequent. We aimed to characterize the inflammatory tumor microenvironment of patients with brain metastasis (BM) progression after IO to gain insight on potential inflammatory resistance mechanisms.
Methods
Patients with BM resection after failure of IO were identified (IO cohort). Tumor-infiltrating lymphocytes (TILs; CD3, CD8, FOXP3) as well as immune checkpoint molecules (PD-L1) were investigated. A control group of BM patients without prior IO was included for comparison (no immunotherapy cohort, NIO).
Results
Twenty-three IO patients (9/23 (39.1%) females, 14/23 (60.9%) males; 11/23 (47.8%) lung cancer patients; 1/23 (4.3%) breast cancer patient; 5/23 (21.7%) melanoma patients; 6/23 (26.1%) patients with other cancer entities) and 79 NIO patients were included in the analyses. Thirteen/23 (56.5%) IO patients showed tumor PD-L1 expression (TPS range 0-100) in BM. FOXP3+ TIL density was statistically significantly higher in IO compared to NIO patients (Mann-Whitney U test; p=0.001, 83.5 cells/mm2 vs. 28.1 cells/mm2). Median CD8+ TIL density was numerically higher in IO (327.0 cells/mm2) compared to NIO (129.8 cells/mm2, p=0.05) whereas median CD3+ TIL density was lower in IO (226.4 cells/mm2) vs. NIO (459.0 cells/mm2, p=0.08) patients, respectively. There was no correlation of time from last IO application to BM resection with TIL density (Spearman correlation coefficient <±0.3).
Conclusions
Higher infiltration with regulatory immunosuppressive FOXP3+ T cells could be an immunological escape mechanism in BM from solid cancers. New immunological targets are warranted to increase the likelihood of response to IO in BM patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Financial support by the Austrian Federal Ministry for Digital and Economic Affairs, the National Foundation for Research, Technology and Development and the Christian Doppler Research Association.
Disclosure
A.M. Starzer: Financial Interests, Personal, Other, Travel support: PharmaMar. M. Preusser: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck Sharp & Dome; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Gerson Lehrman Group; Financial Interests, Personal, Advisory Board: CMC Contrast; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Mundipharma; Financial Interests, Personal, Advisory Board: BMJ Journals; Financial Interests, Personal, Advisory Board: MedMedia; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Medahead; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Tocagen; Financial Interests, Institutional, Sponsor/Funding: Boehringer-Ingelheim; Financial Interests, Institutional, Sponsor/Funding: BMS; Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Institutional, Sponsor/Funding: Merck Sharp & Dome; Financial Interests, Institutional, Sponsor/Funding: Novocure; Financial Interests, Institutional, Sponsor/Funding: GlaxoSmithKline; Financial Interests, Institutional, Sponsor/Funding: AbbVie. A.S. Berghoff: Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Roche; Financial Interests, Personal, Other, Travel support: Amgen; Financial Interests, Personal, Other, Travel support: Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: AbbVie. All other authors have declared no conflicts of interest.