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Suppressed immune microenvironment and repertoire in brain metastases from patients with resected non-small-cell lung cancer

Authors :
J. Zhang
L.M. Solis Soto
Barbara Mino
J. Jack Lee
Alexandre Reuben
I. I. Wistuba
Don L. Gibbons
James G. Fujimoto
A. Vaporcyan
Frederick F. Lang
Jason T. Huse
Dzifa Y. Duose
Humam Kadara
Hitoshi Dejima
Rajyalakshmi Luthra
Sinchita Roy-Chowdhuri
Edwin R. Parra
Norihiko Ikeda
Y. Kudo
Cesar A. Moran
Cara Haymaker
Ronald Abraham
Source :
Ann Oncol
Publication Year :
2019
Publisher :
Oxford University Press, 2019.

Abstract

BACKGROUND: The tumor immune microenvironment (TIME) of lung cancer brain metastasis is largely unexplored. We carried out immune profiling and sequencing analysis of paired resected primary tumors and brain metastases of non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: TIME profiling of archival formalin-fixed and paraffin-embedded specimens of paired primary tumors and brain metastases from 39 patients with surgically resected NSCLCs was carried out using a 770 immune gene expression panel and by T-cell receptor beta repertoire (TCRβ) sequencing. Immunohistochemistry was carried out for validation. Targeted sequencing was carried out to catalog hot spot mutations in cancer genes. RESULTS: Somatic hot spot mutations were mostly shared between both tumor sites (28/39 patients; 71%). We identified 161 differentially expressed genes, indicating inhibition of dendritic cell maturation, Th1, and leukocyte extravasation signaling pathways, in brain metastases compared with primary tumors (P

Details

Language :
English
Database :
OpenAIRE
Journal :
Ann Oncol
Accession number :
edsair.doi.dedup.....b0c4d924bad8ac65a413e4793ad73903