Cutting Edge: Enhanced Antitumor Immunity in ST8Sia6 Knockout Mice

David J. Friedman, Monika Kizerwetter, Paul Belmonte, Matthew Rajcula, Keith Theodore, Hyun Se Kim Lee, Michael J. Shapiro, Haidong Dong, Virginia Smith Shapiro

Research output: Contribution to journalArticlepeer-review

Abstract

Inhibitory receptors have a critical role in the regulation of immunity. Siglecs are a family of primarily inhibitory receptors expressed by immune cells that recognize specific sialic acid modifications on cell surface glycans. Many tumors have increased sialic acid incorporation. Overexpression of the sialyltransferase ST8Sia6 on tumors led to altered immune responses and increased tumor growth. In this study, we examined the role of ST8Sia6 on immune cells in regulating antitumor immunity. ST8Sia6 knockout mice had an enhanced immune response to tumors. The loss of ST8Sia6 promoted an enhanced intratumoral activation of macrophages and dendritic cells, including upregulation of CD40. Intratumoral regulatory T cells exhibited a more inflammatory phenotype in ST8Sia6 knockout mice. Using adoptive transfer studies, the change in regulatory T cell phenotype was not cell intrinsic and depended on the loss of ST8Sia6 expression in APCs. Thus, ST8Sia6 generates ligands for Siglecs that dampen antitumor immunity.

Original languageEnglish (US)
Pages (from-to)1845-1850
Number of pages6
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume208
Issue number8
DOIs
StatePublished - Apr 15 2022

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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