Differences in tumor microenvironments between primary lung tumors and brain metastases in lung cancer patients: therapeutic implications for immune checkpoint inhibitors

BMC Cancer

Doo Hyun Chung¹  Yoon Kyung Jeon¹  Jong Seok Lee²  Yu Jung Kim²  Se Hyun Kim²  Dae Seog Heo³  Dong-Wan Kim³  Ryul Kim³  Tae Min Kim³  Miso Kim³  Bhumsuk Keam³  Jin Wook Kim⁴  Sehui Kim⁵ 

[1] Cancer Research Institute, Seoul National University College of Medicine;Department of Internal Medicine, Seoul National University Bundang Hospital;Department of Internal Medicine, Seoul National University Hospital;Department of Neurosurgery, Seoul National University Hospital;Department of Pathology, Seoul National University Hospital;

关键词: Immunotherapy;    Lung cancer;    Brain metastasis;    PD-1;    PD-L1;   

DOI  :  10.1186/s12885-018-5214-8

来源: DOAJ

【 摘 要 】

Abstract Background We aimed to compare intra- and extracranial responses to immune checkpoint inhibitors (ICIs) in lung cancer with brain metastases (BM), and to explore tumor microenvironments of the brain and lungs focusing on the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Methods Two cohorts of lung cancer patients with BM were analyzed. Cohort 1 included 18 patients treated with nivolumab or pembrolizumab, and intra- and extracranial responses were assessed. Cohort 2 comprised 20 patients who underwent both primary lung surgery and brain metastasectomy. Specimens from cohort 2 were subjected to immunohistochemical analysis for the following markers: CD3, CD4, CD8, FOXP3, and PD-1 on tumor infiltrating lymphocytes (TIL) and PD-L1 on tumor cells. Results Seven patients (38.9%) in cohort 1 showed progressive disease in both primary and intracranial lesions. Although the other 11 patients exhibited a partial response or stable disease in the primary lesion, eight showed a progression in BM. Interestingly, PD-1+ TILs were significantly decreased in BM (P = 0.034). For fifteen patients with adenocarcinoma, more distinctive patterns were observed in CD3+ (P = 0.078), CD8+ (P = 0.055), FOXP3+ (P = 0.016), and PD-1+ (P = 0.016) TILs. Conclusions There may be discordant responses to an ICI of lung cancer between primary lung lesion and BM based on discrepancies in the tumor microenvironment. The diminished infiltration of PD-1+ TILs in tumor tissue within the brain may be one of the major factors that hinder the response to anti–PD-1 antibody in BM.

【 授权许可】

Unknown