Hsp60 in Cancer Immunity: Biological Basis, Diagnostic Potential and Therapeutic Opportunities

The HSP Immune Network in Cancer

“…Highly metastatic B16 cells released higher levels of HSP60 resulting in persistent TLR2 and STAT3 activation compared to poorly metastatic B16-F1 cells ( 148 ). These results provide a mechanistic explanation to the role that extracellular HSP60s play in promoting immunosuppressive tumor microenvironment ( 2 ).…”

“…eHSP60 induces the maturation of bone marrow-derived dendritic cells (BMDCs) via TLR4 and activation of allogeneic T cells, resulting in the production of Th1-promoting cytokines ( 140 ). Feng and colleagues demonstrated that the expression of HSP60 on the surface of apoptotic tumor cells activates DCs and induces cytotoxic T cell response, suggesting that the HSP60 on tumor cells may promote potent anti-tumor T cell response mediated by APC ( 2 , 146 ). By contrast, T cells pre-treated with HSP60 downregulate Th1-associated transcription factors such as T-bet, NFATp and NF-kB, inhibiting the secretion of IFN-γ and TNF-β, and upregulate GATA-3, leading to increased secretion of Th2-associates cytokines such as IL-10, IL-4 and IL-13 ( Figure 2B ) ( 143 ).…”

“…In the extracellular milieu, HSP60 released by B16 melanoma cells promotes the secretion of immunosuppressive cytokines and chemokines including IL-6, IL-10, IL-13, TGF-β1, CCL-2 and CCR8 via TLR2 and STAT3 activation ( 2 , 148 ). Highly metastatic B16 cells released higher levels of HSP60 resulting in persistent TLR2 and STAT3 activation compared to poorly metastatic B16-F1 cells ( 148 ).…”

“…Heat shock proteins (HSPs) are molecular chaperones classified into several families such as HSP70, HSP90, HSP110, HSPB, HSP40 and chaperonins (1). HSPs are induced upon various cellular stresses including heat, radiation, infectious agents, heavy metal toxicity and hypoxia (2). Recent data have emerged suggesting that HSP functions are not only dependent on the stimuli triggering their expression, but also the compartment in which they are present (3)(4)(5)(6)(7)(8)(9).…”

Targeting PRMT3 Impairs Methylation and Oligomerization of HSP60 to Boost Anti-Tumor Immunity by Activating cGAS/STING Signaling

“…Interestingly, HSP60 has been implicated in tumorigenesis as well as modulating immune responses. 35 Thus, we decided to explore whether there is an association between HSP60 expression with HCC tumor progression and immune modulation by analyzing publicly available proteomic 36 and TCGA-LIHC datasets. We found that HSP60 protein was significantly upregulated in HCC tissues compared to adjacent normal tissues (Supplementary Fig.…”