Cell surface targeting of heat shock protein gp96 induces dendritic cell maturation and antitumor immunity

H. Zheng, J. Dai, D. Stoilova, Z. Li

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

gp96 is a residential heat shock protein of the endoplasmic reticulum that has been implicated in the activation of dendritic cells (DCs) for the initiation of adaptive immunity. By genetic targeting of gp96 onto the cell surface, we demonstrate that direct access of gp96 to DCs induces their maturation, resulting in secretion of proinflammatory cytokines IL-1β, IL-12, and chemokine monocyte chemoattractant protein-1 and up-regulation of the expression of MHC class I, MHC class II, CD80, CD86, and CD40. Furthermore, surface expression of gp96 on tumor cells renders them regressive via a T lymphocyte-dependent mechanism. This work reinforces the notion that gp96 is an endogenous DC activator and unveils that the context in which Ag is delivered to the immune system, in this case surface expression of gp96, has profound influence on immunity. It also establishes a principle of bridging innate and adaptive immunity for cancer immunotherapy by surface targeting of an intracellular heat shock protein.

Original languageEnglish (US)
Pages (from-to)6731-6735
Number of pages5
JournalJournal of Immunology
Volume167
Issue number12
DOIs
StatePublished - Dec 15 2001

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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