Aggressive Behavior in Silent Subtype III Pituitary Adenomas May Depend on Suppression of Local Immune Response: A Whole Transcriptome Analysis

Timothy E. Richardson, Zhong Jian Shen, Mohammed Kanchwala, Chao Xing, Alexander Filatenkov, Ping Shang, Samuel Barnett, Zahidur Abedin, James S. Malter, Jack M. Raisanen, Dennis K. Burns, Charles L. White, Kimmo J. Hatanpaa

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Silent subtype III pituitary adenomas (SS-3) are clinically nonfunctional adenomas that are more aggressive in terms of invasion and risk of recurrence than their conventional null cell counterparts. We previously showed that these tumors can be distinguished by immunohistochemistry based on the identification of a markedly enlarged and fragmented Golgi apparatus. To understand the molecular correlates of differential aggressiveness, we performed whole transcriptome sequencing (RNAseq) on 4 SS-3 and 4 conventional null cell adenomas. The genes that were highly upregulated in all the SS-3 adenomas included 2 secreted proteins involved in the suppression of T-lymphocyte activity, i.e., ARG2 (multiple testing adjusted padj = 1.5 × 10-3) and SEMA3A (padj = 3.3 × 10-3). Highly downregulated genes in all the SS-3 adenomas included HLA-B (padj = 3.3 × 10-6), suggesting reduced antigen presentation by the adenoma to cytotoxic T-cells. Quantitative RT-PCR of these genes performed on the adenoma samples supported the RNAseq results. We also found a relative decrease in the overall concentration of T-lymphocytes in the SS-3 tumors. These results suggest that SS-3 adenomas actively suppress the immune system and raise the possibility that they may be treatable with immune checkpoint inhibitors or nonspecific cancer immunotherapies.

Original languageEnglish (US)
Pages (from-to)874-882
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume76
Issue number10
DOIs
StatePublished - Oct 1 2017

Keywords

  • ARG2
  • HLA-B
  • Null cell adenoma
  • Pituitary adenoma
  • SEMA3A
  • Silent subtype III
  • Transcriptome sequencing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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