Characterization of the immune microenvironment in brain metastasis from non-small cell lung cancer

Purpose Brain metastases can induce life-threatening events and their immune microenvironment is still unrevealed. To elucidate the probability of immune-oncology therapy for brain metastases, we utilized immune profiling of resected brain metastases and paired non-small cell lung cancer (NSCLC). Methods To compare pure tumor-infiltrating lymphocytes (TILs) or tumor tissues between NSCLC and brain metastases, macro-dissection was performed before extracting DNA and RNA from 39 patients who received surgical resection of local NSCLC tumor lesions and brain metastases from matched patients. We applied gene expression analysis of mRNA by using a 770 gene panel related with cancer immune cells. Targeted sequencing of 50 cancer hotspot genes on extracted DNA was performed for genotyping. TCRs sequencing of extracted DNA was utilized for profiling of TCR repertoire. Results We identified 161 differentially expressed genes, which reflected inhibition of dendritic cell maturation pathway, Th1 pathway, and leukocyte extravasation signaling pathway in brain metastases (p Conclusion The microenvironment in brain metastases from NSCLC was revealed to be immunosuppressive, with the majority of T-cell clones in brain metastases being shared with the primary lesion. Citation Format: Yujin Kudo, Cara Haymaker, Jiexin Zhang, Alexandre Reuben, Dzifa Yawa Duose, Junya Fujimoto, Sinchita Roy-Chowdhuri, Luisa Maren Solis, Hitoshi Dejima, Edwin Roger Cuentas, Barbara Mino, Ronald Abraham, Norihiko Ikeda, Rajyalakshmi Luthra, Jack J. Lee, Humam Kadara, Jason T. Huse, Ignacio I. Wistuba. Characterization of the immune microenvironment in brain metastasis from non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2790.