Senescence, immune microenvironment, and vascularization in cardiac myxomas

Cardiovasc Pathol. 2021 May-Jun:52:107335. doi: 10.1016/j.carpath.2021.107335. Epub 2021 Mar 21.

Abstract

Aims: Cardiac myxomas are rare tumors of incompletely elucidated pathogenesis. The aim of this study is to explore the possible presence of a senescence phenotype in cardiac myxomas, associated with an inflammatory and vasculogenic tumor microenvironment.

Methods and results: This is a retrospective study of 29 cardiac myxomas with immunohistochemical detection of various inflammatory, vascular, and senescence markers. We show that all myxomas contain tumor cells in senescence overexpressing p16, and a fraction of senescent endothelial cells. Macrophages are the principal inflammatory cell population, followed by cytotoxic T cells, with fewer plasma cells, mastocytes, and B lymphocytes. These populations are found in different intratumoral localizations. Larger tumor volume is associated with a lower percentage of myxoid matrix, higher cellularity, higher macrophage, and lower number of mast cells as well as higher PD-L1 expression by inflammatory cells. Higher vascular density is associated with higher percentage of B cells, a lower number of macrophages and higher number of mastocytes, and lower PD-L1 expression by inflammatory cells. Tumors with higher vascular density and higher cellularity show higher amounts of p16 senescent endothelial cells.

Conclusions: Myxoma tumor cells are in senescence and reside inside a tumor microenvironment with a distinct inflammatory profile rich in macrophages and cytotoxic T cells, and a rich vasculature, probably attributed to a senescence-associated secretory phenotype.

Keywords: PD-L1; SASP; cardiac tumors; lymphocytes; macrophages; mast cells; myxoma; p16; rare tumors; vascular density.

MeSH terms

  • B7-H1 Antigen
  • Endothelial Cells
  • Heart Neoplasms* / immunology
  • Heart Neoplasms* / pathology
  • Humans
  • Myxoma* / immunology
  • Myxoma* / pathology
  • Neovascularization, Pathologic
  • Retrospective Studies
  • Senescence-Associated Secretory Phenotype
  • Tumor Microenvironment / immunology

Substances

  • B7-H1 Antigen