4.6 Article

Characterization of the immune microenvironment in brain metastases from different solid tumors

Journal

CANCER MEDICINE
Volume 9, Issue 7, Pages 2299-2308

Publisher

WILEY
DOI: 10.1002/cam4.2905

Keywords

brain metastasis; immune checkpoint; immune system; lymphocyte; PD-L1

Categories

Funding

  1. National Science Foundation of China [81972707, 81672327, 81502013, 81602411]
  2. Program of Shanghai Academic/Technology Research Leader [17XD1402600]
  3. Program for Outstanding Medical Academic Leader
  4. Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20161410]
  5. [SHDC12017X06]

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Background Brain metastases are one of the most common intracranial neoplasms. Increasing evidence have indicated that systemic immunotherapy may provide long-term benefits for brain metastases. Herein, we presented the results of an immune oncology panel RNA sequencing platform for patients with brain metastases from different primary sites. Methods We investigated 25 samples of human brain metastases from lung cancer (n = 12), breast cancer (n = 6), and colorectal cancer (n = 7). Besides, 13 paired samples of adjacent noncancerous brain tissue (10 from patients with lung cancer and 3 from patients with breast cancer) were collected as controls. By comparing the brain metastases and paired samples of adjacent noncancerous brain tissue from 13 patients, we detected three upregulated and six downregulated genes, representing the malignant properties of cancer cells and increased immune infiltration in the microenvironment. Next, we profiled the immune-related genes in brain metastases from three primary cancer types. Results A group of genes were significantly overexpressed in the microenvironment of brain metastases from lung cancer, covering the checkpoint pathways, lymphocyte infiltration, and TCR-coexpression. Especially, immune checkpoint molecules, PD-L1, PD-L2, and IDO1 were expressed at higher levels in brain metastases from lung cancer than those from the other two cancer types. Conclusions This study presents an immune landscape of brain metastases from different cancer types. With high RNA expression levels of PD-1/PD-L1 axis and immune infiltration in brain metastases, it would be worthwhile to explore the efficacy of immune checkpoint blockade for lung cancer patients with intracranial metastases.

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