Enhancing the treatment effect on melanoma by heat shock protein 70-peptide complexes purified from human melanoma cell lines

Gao, Yumei; Gao, Weishi; Chen, Xia; Cha, Nier; Wang, Xiaoli; Xing, Jia; Wang, Bingping; Ren, Meng; Ren, Jun

doi:10.3892/or.2016.4947

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…CD8 + T cells are an important component of the tumour immune response and exert cytotoxic effects on melanoma cells ( Durgeau et al, 2018 ). Dendritic cell tumour vaccines are the earliest and most effective methods for the clinical treatment of melanoma ( Gao et al, 2016 ). Furthermore, the neutrophil-to-lymphocyte ratio can be used as a biomarker for metastatic SKCM ( Sellers et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Yang

Che

et al. 2022

Front. Genet.

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Background: Skin cutaneous melanoma (SKCM) is a common malignancy that is associated with increased morbidity and mortality. Complement C1Q is composed of C1QA, C1QB, and C1QC and is involved in the occurrence and development of many malignant tumours. However, the effect of C1QA, C1QB, and C1QC expression on tumour immunity and prognosis of cutaneous melanoma remains unclear.Methods: First, we analysed C1QA, C1QB, and C1QC expression levels and prognostic values using Gene Expression Profiling Interactive Analysis (GEPIA) and Tumour Immune Estimation Resource (TIMER) analysis, and further validation was performed using RT-qPCR, The Human Protein Atlas, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus dataset. We then performed univariate/multivariate Cox proportional hazard model, clinicopathological correlation, and receiver operating characteristic curve analysis using TCGA dataset and established a nomogram model. Differentially expressed genes associated with C1QA, C1QB, and C1QC in SKCM were identified and analysed using LinkedOmics, TIMER, the Search Tool for the Retrieval of Interacting Genes database, and Metascape and Cytoscape software platforms. We used TIMER, GEPIA, and single-sample gene set enrichment analysis (ssGSEA) to analyse the relationship between the three genes and the level of immune cell infiltration, biomarkers, and checkpoint expression in SKCM. Finally, GSEA was utilized to study the functional pathways of C1QA, C1QB, and C1QC enrichment in SKCM.Results: The overexpression of C1QA, C1QB, and C1QC provided significant value in the diagnosis of SKCM and has been associated with better overall survival (OS). Multivariate Cox regression analysis indicated that C1QA, C1QB, and C1QC are independent prognostic biomarkers for patients with SKCM. Immune cell infiltration, biomarkers, and checkpoints were positively correlated with the expression of C1QA, C1QB, and C1QC. Furthermore, the results of functional and pathway enrichment analysis showed that immune-related and apoptotic pathways were significantly enriched in the high-expression group of C1QA, C1QB, and C1QC.Conclusion: We found that C1QA, C1QB, and C1QC can be used as biomarkers for the diagnosis and prognosis of SKCM patients. The upregulated expression levels of these three complement components benefit patients from OS and may increase the effect of immunotherapy. This result may be due to the dual effects of anti-tumour immunity and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Yang

Che

et al. 2022

Front. Genet.

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“…A commonly used method is to differentiate MNCs into imDCs by cultivation in GM-CSF and IL-4 medium for 3 to 7 days and then add TNF-α, IL-1, lipopolysaccharide, or monocyte conditioned culture solution to induce DC maturation. [14][15][16] However, toxicity is a principal restriction of some agents, such as lipopolysaccharide and TNF-α. 17 The primary response factor in tumor control is MHC-Irestricted CTLs.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, culture and induction in vitro are necessary to obtain a large number of DCs to meet the needs of clinical treatment. A commonly used method is to differentiate MNCs into imDCs by cultivation in GM-CSF and IL-4 medium for 3 to 7 days and then add TNF-α, IL-1, lipopolysaccharide, or monocyte conditioned culture solution to induce DC maturation 14–16. However, toxicity is a principal restriction of some agents, such as lipopolysaccharide and TNF-α 17…”

Section: Discussionmentioning

confidence: 99%

Effect of BCG HSP70 Gene Transfection on Dendritic Cells Derived From Bone Marrow in Children With Acute Leukemia

Wang

et al. 2022

Journal of Pediatric Hematology/Oncology

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Objectives: In this study, immature dendritic cells (imDCs) were transfected with the Bacillé Calmette-Guérin (BCG) heat shock protein 70 (HSP70) gene to investigate the impact on the maturity and function of imDCs from the bone marrow of pediatric patients with acute leukemia. Materials and Methods: Bone marrow mononuclear cells were isolated from pediatric patients with acute lymphoblastic leukemia who had achieved complete remission at least 6 months prior. The recombinant vector pDisplay-HSP70 was transfected into imDCs. The test groups included 5 subgroups: imDCs (imDCs without special processing), imDC-neos (imDCs transfected with the pDisplay vector), HSP70 (imDCs transfected with the pDisplay-HSP70 vector), tumor necrosis factor α (TNF-α) (imDCs induced with rhTNF-α), and HSP70+TNF-α. Mature dendritic cells (mDCs) from different groups (HSP70, TNF-α, and HSP70+TNF-α) and T cells were cultured. An equal number of lymphocytes and mDCs were used as controls. The proliferation indices of T cells and the cytokine contents (interleukin-12 and interferon-γ) were determined. Results: The HSP70 group and the TNF-α group expressed higher levels of HLA-DR, CD80, and CD86 but lower levels than the HSP70+TNF-α group; there was no significant difference between the HSP70 group and the TNF-α group. The combination of HSP70 and TNF-α induced the highest levels of interleukin-12 and interferon-γ. Conclusions: The outcomes of this study indicated that gene transfection with BCG HSP70 evidently promoted imDC maturity and the antitumor effects of mDC-mediated T cells. It could serve as a candidate gene-modified cell vaccine for tumor immunotherapy.

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“…In summary, immunotherapy has emerged as a prominent modality in the treatment of tumors ( 34 ). For the first time, the present study shows that anti-CTLA-4 Nb16 has an intrinsic value for delaying melanoma tumor.…”

Section: Discussionmentioning

confidence: 99%

Screening and antitumor effect of an anti‑CTLA‑4 nanobody

et al. 2017

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Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a critical negative regulator of immune responses. CTLA-4 is rapidly upregulated following T-cell activation, and then binds to B7 molecules with a higher affinity than CD28. CTLA-4 may abolish the initiation of the responses of T cells by raising the threshold of signals required for full activation of T cells, and it also may terminate ongoing T-cell responses. This regulatory role has led to the development of monoclonal antibodies (mAbs) designed to block CTLA-4 activity for enhancing immune responses against cancer. mAbs have several disadvantages including high production cost and unstable behavior. Nanobodies (Nbs) are single-domain antigen-binding fragments derived from the camelid heavy-chain antibodies, which are highly attractive in cancer immunotherapy due to their small size, high specificity, and stability. We selected CTLA-4-specific Nbs from a high quality dromedary camel immune library by phage display technology. Four positive colonies were sequenced and classified based on the amino acids sequences in the CDR3 region. These Nbs recognized unique epitopes on CTLA-4 and displayed high binding rates when used on PHA-stimulated human T cells. Treatment of B16 melanoma-bearing C57BL/6 mice with anti-CTLA-4 nanobody 16 (Nb16) delayed melanoma growth and prolonged the survival time of mice. These data indicate that anti-CTLA-4 Nbs selected from a high quality phage display library may be effective for the treatment of patients with tumors.

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Enhancing the treatment effect on melanoma by heat shock protein 70-peptide complexes purified from human melanoma cell lines

Cited by 9 publications

References 26 publications

Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Effect of BCG HSP70 Gene Transfection on Dendritic Cells Derived From Bone Marrow in Children With Acute Leukemia

Screening and antitumor effect of an anti‑CTLA‑4 nanobody

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