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Review
. 2021 Nov 30:12:796493.
doi: 10.3389/fimmu.2021.796493. eCollection 2021.

The HSP Immune Network in Cancer

Zarema Albakova  1 , Yana Mangasarova  2
Affiliations
Review

The HSP Immune Network in Cancer

Zarema Albakova et al. Front Immunol. .

Abstract

Heat shock proteins are molecular chaperones which support tumor development by regulating various cellular processes including unfolded protein response, mitochondrial bioenergetics, apoptosis, autophagy, necroptosis, lipid metabolism, angiogenesis, cancer cell stemness, epithelial-mesenchymal transition and tumor immunity. Apart from their intracellular activities, HSPs have also distinct extracellular functions. However, the role that HSP chaperones play in the regulation of immune responses inside and outside the cell is not yet clear. Herein, we explore the intracellular and extracellular immunologic functions of HSPs in cancer. A broader understanding of how HSPs modulate immune responses may provide critical insights for the development of effective immunotherapies.

Keywords: cancer; extracellular HSPs; heat shock proteins; immunotherapy; tumor immunity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Extracellular HSP70 immune network in cancer. eHSP70s enhance NK cytotoxicity, DC maturation, induce strong CD4+ and CD8+ T cell responses and cytokine secretion by monocytes and enhance immunosuppressive activity of MDSCs and T regs (, –118). MDSCs, myeloid-derived suppressor cells; T reg, T regulatory cell; GzmB, granzyme B; DC, dendritic cells; IFNγ, interferon γ; BAG, BCL2-associated athanogene; IL-6, interleukin-6; TNF-α, tumor necrosis factor α; VEGF, vascular endothelial growth factor; TGF-β, transforming growth factor β; PI3K/AKT, phosphatidylinositol 3-kinase (PI3K)-serine/threonine protein kinase (AKT), JNK, c-Jun N-terminal kinase; STAT3, signal transducer and activator of transcription.
Figure 2
Figure 2
Extracellular HSP60 immune network. (A) HSP60 induces DC maturation and secretion of inflammatory cytokines (–142). (B) eHSP60 downregulates Th1-associated transcription factors (T-bet, NF-kB, NFATp) and upregulates GATA3, leading to decreased secretion of TNF-α and IFN-γ and increased secretion of IL-10, IL-4, IL-13 (143). Activated T cells can present HSP60 via MHC molecules to anti-ergotypic T cells, leading to the production of IFNγ and TGFβ1 by anti-ergotypic T regulatory cells (144). (C) HSP60 activates B cells via TLR4-MyD88 signaling pathway, leading to the production of IL-10, IL-6 and IgG3 (145). TLR4, Toll-like receptor 4; NO, nitric oxide, CD40L; CD40 ligand; TCR, T cell receptor; MHC II, major histocompatibility complex; IgG3, Immunoglobulin G3; Nf-kB; nuclear factor kappa B; NFAT, nuclear factor of activated T cells.
See this image and copyright information in PMC

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