Dataset Information

Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer.

ABSTRACT: Background:Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored. Results:The median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1-70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, P < 0.01). The numbers of CD4/CD8/Foxp3-positive cells were significantly higher in primary breast tumors than in brain metastases (paired t-test, P < 0.05 for all antibodies). In patients with triple-negative breast cancer specifically, low TIL numbers were associated with significantly shorter overall survival compared to high TIL numbers (log-rank test, P = 0.04). Materials and Methods:We retrospectively identified 107 patients with breast cancer and brain metastases who had undergone surgery between 2001 and 2012 at 8 institutions, and collected 191 samples including brain metastases alone and primary tumors with pair-matched brain metastasis samples. Hematoxylin and eosin-stained slides were evaluated for TILs and categorized according to the extent of staining. Immunohistochemistry for CD4, CD8, Foxp3, PD-L1, PD-L2, and HLA class I was also performed. Conclusions:There are significantly fewer TILs in brain metastases than in primary breast tumors.

SUBMITTER: Ogiya R

PROVIDER: S-EPMC5732758 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer.

Ogiya Rin R Niikura Naoki N Kumaki Nobue N Yasojima Hiroyuki H Iwasa Tsutomu T Kanbayashi Chizuko C Oshitanai Risa R Tsuneizumi Michiko M Watanabe Ken-Ichi KI Matsui Akira A Fujisawa Tomomi T Saji Shigehira S Masuda Norikazu N Tokuda Yutaka Y Iwata Hiroji H

Oncotarget 20171027 61

<h4>Background</h4>Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored.<h4>Results</h4>The median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1-70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, <i>P</i> < 0.01). The numbers of CD4 ...[more]

PMID: 29262592

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Project description:We performed RNA-seq to investigate the differences in the gene expression profiles between primary gastric cancer (PGC) and paired metastatic gastric cancer (MGC). RNA-sequencing was performed on 7 paired PGC and MGC FFPE tissues. The transcriptome profiling of the two groups (MGC vs PGC) including immune response gene signature was analyzed. Total RNA was isolated using Trizol reagent. Extracted RNA samples were processed using the QuantSeq 3’mRNA-Seq Library Prep Kit and sequenced on an Illumina NextSeq 500. QuantSeq 3’mRNA-Seq reads were aligned using Bowtie2. The alignment file was used to assemble transcripts and the Read Count data was processed based on quantile normalization method using EdgeR within R. We identified 519 differentially regulated genes between the two sets, 76 of which were significantly up-regulated and 443 significantly down-regulated in MGCs. Among DEGs, 33 immune response genes were selected using QuickGO database (https://www.ebi.ac.uk/QuickGO/), with majority (27/33) of them exhibiting downregulation in the MGC samples. In summary, RNA sequencing data revealed that immune-related gene expression were down-regulated in MGC compared to PGC. We performed RNA-seq to investigate the differences in the gene expression profiles between primary gastric cancer (PGC) and paired metastatic gastric cancer (MGC). RNA-sequencing was performed on 7 paired PGC and MGC FFPE tissues. The transcriptome profiling of the two groups (MGC vs PGC) including immune response gene signature was analyzed. Total RNA was isolated using Trizol reagent. Extracted RNA samples were processed using the QuantSeq 3’mRNA-Seq Library Prep Kit and sequenced on an Illumina NextSeq 500. QuantSeq 3’mRNA-Seq reads were aligned using Bowtie2. The alignment file was used to assemble transcripts and the Read Count data was processed based on quantile normalization method using EdgeR within R. We identified 519 differentially regulated genes between the two sets, 76 of which were significantly up-regulated and 443 significantly down-regulated in MGCs. Among DEGs, 33 immune response genes were selected using QuickGO database (https://www.ebi.ac.uk/QuickGO/), with majority (27/33) of them exhibiting downregulation in the MGC samples. In summary, RNA sequencing data revealed that immune-related gene expression were down-regulated in MGC compared to PGC.

Dataset Information

Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer.

Publications

Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer.

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