Hsp70-Like Protein 1 Fusion Protein Enhances Induction of Carcinoembryonic Antigen–Specific CD8+ CTL Response by Dendritic Cell Vaccine

Wu, Yanfeng; Wan, Tao; Zhou, Xiangyang; Wang, Baomei; Yang, Feng; Li, Nan; Chen, Guoyou; Dai, Sheng‐Ming; Liu, Shuxun; Zhang, Minghui; Cao, Xuetao

doi:10.1158/0008-5472.can-04-3912

Cited by 59 publications

(47 citation statements)

References 44 publications

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“…12,13,39 Moreover, a CEA 576-669 -HSP70L1 fusion protein promotes the secretion of Th1 cytokines (such as IL-12 and IFN-c) and stimulates an anti-tumor cytotoxic T lymphocyte response to a DC vaccine. 40 Thus, certain types of chemotherapy can kill tumor cells through efficient cytotoxic effects while enhancing the induction of an anti-tumor immune response.…”

Section: Discussionmentioning

confidence: 99%

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

et al. 2013

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The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design of more efficient protocols for cancer chemoimmunotherapy. It is well known that danger-associated molecular patterns (DAMPs) can activate immune cells, including dendritic cells (DCs), via Toll-like receptors (TLRs); however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of the immune response needs to be further elucidated. Here, we found that colorectal cancer (CRC) cells treated with oxaliplatin (OXA) and/or 5-fluorouracil (5-Fu) released high levels of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70). After OXA/5-Fu therapy, the sera of CRC patients also exhibited increased levels of HMGB1 and HSP70, both of which are well-known DAMPs. The supernatants of dying CRC cells treated with OXA/5-Fu promoted mouse and human DC maturation, with upregulation of HLA-DR, CD80 and CD86 expression and enhancement of IL-1b, TNF-a, MIP-1a, MIP-1b, RANTES and IP-10 production. Vaccines composed of DCs pulsed with the supernatants of chemically stressed CRC cells induced a more significant IFN-c-producing Th1 response both in vitro and in vivo. However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-c-producing Th1 response in TLR4-deficient DCs. Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs via TLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs.

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Section: Discussionmentioning

confidence: 99%

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

et al. 2013

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“…The local production of cytokines (TNF-α, IL-1 and IL-6) by lung tissues in response to infectious or inflammatory stimuli may also attract immune cells, such as neutrophils, dendritic cells and monocytes, to the inflammatory sites (26,27), leading to pulmonary injury. The cytokines also activate granulocytes, which cause acute neutrophilic inflammation and attract natural killer cells, monocytes and a variety of other immune cells (28,29).…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model

Xian

Zhang

Duan

et al. 2014

Molecular Medicine Reports

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Abstract.Triptolide is one of the main active components in the Chinese herb Tripterygium wilfordii Hook F, which has been demonstrated to possess anti-inflammatory properties. The aim of this study was to investigate the effects of triptolide on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to explore the possible mechanisms. Mice were administered LPS intranasally to induce lung injury, and triptolide was administered intraperitoneally 1 h prior to the LPS challenge. Triptolide-treated mice exhibited significantly reduced levels of leukocytes, myeloperoxidase activity and edema of the lung, as well as tumour necrosis factor-α, interleukin (IL)-1β and IL-6 production in the bronchoalveolar lavage fluid compared with LPS-treated mice. Additionally, western blot analysis showed that triptolide inhibited the LPS-induced phosphorylation of nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor-α and nuclear factor κ-light-chain-enhancer of activated B cells-p65 (NF-κB p65) and the expression of Toll-like receptor 4 (TLR4). In conclusion, the results from the present study suggest that the anti-inflammatory effect of triptolide against LPS-induced ALI may be due to its ability to inhibit the TLR4-mediated NF-κB signalling pathway. Triptolide may therefore be a promising potential therapeutic agent for ALI treatment, which may ultimately aid the clinical therapy for patients with ALI.

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“…Accordingly, the rare alleles of the HSPA14 SNPs reported here could be hypothesized to enhance such activity and, thus, avoid accumulation of newly translated proteins during aging. However, hsp14 also enhances cellular immunity in dendrites, e.g., stimulating secretion of for instance IL12 and TNFα, and has therefore been suggested as an adjuvant for the treatment of cancer and infectious disease (Wu et al 2005). An enhancement of such effects could intuitively be considered to pose a positive effect on longevity, although the connection between immune regulatory processes and longevity is, as explained below, probably not that straightforward.…”

Section: Discussionmentioning

confidence: 99%

Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

Soerensen

Dato

Tan

et al. 2012

AGE

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Hsp70-Like Protein 1 Fusion Protein Enhances Induction of Carcinoembryonic Antigen–Specific CD8+ CTL Response by Dendritic Cell Vaccine

Cited by 59 publications

References 44 publications

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model

Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

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