Abstract

Abstract Metastatic brain tumor is the most common form of adult central nervous system (CNS) tumor, and the majority of the cerebral metastasis originate from lung cancer. Along with recent combination strategies applying immune checkpoint inhibitor, evaluating tumor microenvironment of the brain metastasis (BM) needs to be unveiled. In this study, we tried to disclose immune context information of BM of non-small cell lung cancer (NSCLC) by using highly multiplex NanoString digital spatial profiling (DSP) method. Seven cases of NSCLC and metastatic brain tumor were evaluated. To detect proteins at quantitative and high multiplex with spatial resolution, NanoString optical barcoding technology was used to digitally profile protein expression in FFPE samples. Immuno-oncology protein targets, including immune cell markers and checkpoint proteins are included. DSP identified differentially expressed proteins between primary NSCLC and BM. Proteins associated with immune regulation, evasion, and adaptive immunity, such as IDO-1, PD1, PDL1, STAT3, PTEN, and CD44 revealed decreased expression in patients with BM (P<0.01). The expression of pS6 was significantly increased in BM (P<0.01), which is associated with activation induced T-cell death. This study demonstrated differentially expressed proteins in BM associated with immune regulation and evasion via NanoString DSP platform. This study highlighted the localized expression of immune-related proteins of BM in patients with NSCLC. Moreover, our results presented the possibility of using digitally quantified and spatially allocated novel method in BM eliminating the subjectivity and variability associated with the immunohistochemistry techniques. Citation Format: Tae Jung Kim. Quantitative digital spatial protein profiling of non-small cell lung cancer brain metastasis [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A04.

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