Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies

Br J Cancer. 2018 Jul;119(1):105-113. doi: 10.1038/s41416-018-0125-7. Epub 2018 Jun 14.

Abstract

Background: Paraneoplastic neurological syndromes are rare conditions where an autoimmune reaction against the nervous system appears in patients suffering from a tumour, but not linked to the spreading of the tumour. A break in the immune tolerance is thought to be the trigger.

Methods: The transcriptomic profile of 12 ovarian tumours (OT) from patients suffering from paraneoplastic cerebellar degeneration (PCD) linked to anti-Yo antibodies (anti-Yo PCD OT) was compared with 733 ovarian tumours (OT control) from different public databases using linear model analysis.

Results: A prominent significant transcriptomic over-representation of CD8+ and Treg cells was found in anti-Yo PCD OT, as compared to the OT control. However, the overall degree of immune cell infiltration was similar, according to the ESTIMATE immune score. We also found an under-representation of M2 macrophages in anti-Yo PCD OT. Furthermore, the differentially expressed genes were enriched for AIRE-related genes, a well-known transcription factor associated with a broad range of autoimmune diseases. Finally, we found that the differentially expressed genes were correlated to the transcriptomic profiling of the cerebellar structures.

Conclusions: Our data pinpointed the enrichment of acquired immune response, particularly high density of CD8+ lymphocytes, and high-level expression of CDR-related antigens in anti-Yo PCD OT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIRE Protein
  • Aged
  • Aged, 80 and over
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Humans
  • Microarray Analysis
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / immunology
  • Ovarian Neoplasms / complications
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Paraneoplastic Cerebellar Degeneration / complications
  • Paraneoplastic Cerebellar Degeneration / genetics*
  • Paraneoplastic Cerebellar Degeneration / immunology
  • Paraneoplastic Cerebellar Degeneration / pathology
  • T-Lymphocytes, Regulatory / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcriptome / genetics*
  • Transcriptome / immunology

Substances

  • CDR2 protein, human
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Transcription Factors