Roles, Mechanisms, and Opportunities of Heat Shock Protein gp96/grp94 in Infections and Inflammation-Associated Malignancies

  • Songdong Meng
  • Zihai Li


Heat shock proteins (HSP) gp96 (grp94) play an important role in modulating innate and T cell immunity via interaction with toll-like receptors (TLRs) and chaperoning antigenic peptides for antigen presentation to MHC molecules. These immunological properties of gp96 have inspired development of gp96-based prophylactic and therapeutic vaccines against various pathogens, including influenza virus, human papillomavirus, Mycobacterium tuberculosis, hepatitis B virus, and herpes simplex virus in mice models. Besides the already known underlying counterback mechanisms, the intrinsic characteristic of gp96 that simultaneously induce both effector T cell response and regulatory T cells (Tregs) may account for the modest efficiency of gp96-based immunotherapy against chronic infections and cancer. There is thus a strong need for identifying novel combination strategies (e.g., Treg inhibition, and immune checkpoint targeting) for designing a more effective gp96-based vaccine against pathogen infections. In addition, targeting cell membrane gp96 might provide a novel therapeutic approach as certain pathogens induce translocation of endoplasmic reticulum-resided gp96 to cell surface. Placenta-derived gp96 has the ability to initiate antitumor T-cell immunity via association with multiple embryo-cancer antigens against chronic infection-associated cancers. Further understanding of the placental gp96 associated-carcinoembryonic antigen repertoires that orchestrate immune defense networks against pathogen-induced cancer formation may allow ample opportunities to provide an effective strategy in cancer prevention and therapy.


Heat shock protein gp96 T cell immunity Toll-like receptors Treg Vaccine Adjuvant Immunotherapy 



Alanine aminotransaminase


Antigen-presenting cell


Bacillus Calmette-Guerin

Con A

Concanavalin A


Cytotoxic T lymphocyte


Cytotoxic T lymphocyte-associated antigen-4


Dendritic cell




Forkhead/winged helix transcription factor


Hepatitis B core antigen


Hepatitis B surface antigen


Hepatitis B virus


Hepatocellular carcinoma


Hepatitis C virus


Human papillomavirus


Heat shock protein


Herpes simplex virus






Monoclonal antibody


Major histocompatibility complex


Muramyl dipeptide


Mitogen-activated protein kinase


NLR family, pyrin domain containing 3


Programmed death-1


Programmed death 1 ligand 1


Transporter associated with antigen processing




Toll like receptor


Tumor necrosis factor


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Key Laboratory of Pathogenic Microbiology and Immunology, Institute of MicrobiologyChinese Academy of SciencesBeijingChina
  2. 2.Hollings Cancer Center, Department of Microbiology and ImmunologyMedical University of South CarolinaCharlestonUSA

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