Synergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies

Medina-Echeverz, José; Hinterberger, Maria; Testori, Marco; Geiger, Marlene; Giessel, Raphael; Bathke, Barbara; Kassub, Ronny; Gräbnitz, Fabienne; Fiore, Giovanna; Wennier, Sonia; Chaplin, Paul; Suter, Mark; Hochrein, Hubertus; Lauterbach, Henning

doi:10.1038/s41467-019-12998-6

Cited by 39 publications

(27 citation statements)

References 67 publications

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“…GO203, targeting MUC1-C, can suppress PD-L1 expression of NSCLC and breast cancer, and induces effectors of innate and adaptive immunity, resulting in improve anticancer effects [31] We determined that evodiamine can block PD-L1 expression on mRNA and protein levels, perhaps through inhibiting the MUC1-C. Silencing MUC1-C in H1975 decreases apoptosis following evodiamine treatment. Currently, several preclinical and clinical trials for the combination of other therapy with immune inhibitors in the treatment patients reveal biomarkers of response and resistance to anti-PD-1 monotherapy and combined anti-CTLA-4 and anti-PD-1 immunotherapy, significantly improve the anti-tumor effect [6,[58][59][60][61]. Collectively, the combination of evodiamine and PD-1 mAb treatment enhance anti-cancer and survival in a Lewis lung carcinoma model.…”

Section: Discussionmentioning

confidence: 99%

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

Jiang

Huang

Xie

et al. 2020

J Exp Clin Cancer Res

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Background Accumulating evidence showed that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Programmed Death Ligand 1 (PD-L1) is expressed in many cancer cell types, while its binding partner Programmed Death 1 (PD1) is expressed in activated T cells and antigen-presenting cells. Whereas, its dysregulation in the microenvironment is poorly understood. In the present study, we confirmed that evodiamine downregulates MUC1-C, resulting in modulating PD-L1 expression in non-small cell lung cancer (NSCLC). Methods Cell viability was measured by MTT assays. Apoptosis, cell cycle and surface PD-L1 expression on NSCLC cells were analyzed by flow cytometry. The expression of MUC1-C and PD-L1 mRNA was measured by real time RT-PCR methods. Protein expression was examined in evodiamine-treated NSCLC cells using immunoblotting or immunofluorescence assays. The effects of evodiamine treatment on NSCLC sensitivity towards T cells were investigated using human peripheral blood mononuclear cells and Jurkat, apoptosis and IL-2 secretion assays. Female H1975 xenograft nude mice were used to assess the effect of evodiamine on tumorigenesis in vivo. Lewis lung carcinoma model was used to investigate the therapeutic effects of combination evodiamine and anti-PD-1 treatment. Results We showed that evodiamine significantly inhibited growth, induced apoptosis and cell cycle arrest at G2 phase of NSCLC cells. Evodiamine suppressed IFN-γ-induced PD-L1 expression in H1975 and H1650. MUC1-C mRNA and protein expression were decreased by evodiamine in NSCLC cells as well. Evodiamine could downregulate the PD-L1 expression and diminish the apoptosis of T cells. It inhibited MUC1-C expression and potentiated CD8+ T cell effector function. Meanwhile, evodiamine showed good anti-tumor activity in H1975 tumor xenograft, which reduced tumor size. Evodiamine exhibited anti-tumor activity by elevation of CD8+ T cells in vivo in Lewis lung carcinoma model. Combination evodiamine and anti-PD-1 mAb treatment enhanced tumor growth control and survival of mice. Conclusions Evodiamine can suppress NSCLC by elevating of CD8+ T cells and downregulating of the MUC1-C/PD-L1 axis. Our findings uncover a novel mechanism of action of evodiamine and indicate that evodiamine represents a potential targeted agent suitable to be combined with immunotherapeutic approaches to treat NSCLC cancer patients. MUC1-C overexpression is common in female, non-smoker, patients with advanced-stage adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

Jiang

Huang

Xie

et al. 2020

J Exp Clin Cancer Res

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“…T cell-based cancer immunotherapy, including checkpoint suppression or adoptive cell therapy, has greatly revolutionized cancer treatment 37 . It is also well known that immunity plays a significant role in the occurrence and development of tumors.…”

Section: Resultsmentioning

confidence: 99%

Identification of prognostic biomarkers related to the tumor microenvironment in thyroid carcinoma

et al. 2021

Sci Rep

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Thyroid Carcinoma (THCA) is the most common endocrine tumor that is mainly treated using surgery and radiotherapy. In addition, immunotherapy is a recently developed treatment option that has played an essential role in the management of several types of tumors. However, few reports exist on the use of immunotherapy to treat THCA. The study downloaded the miRNA, mRNA and lncRNA data for THCA patients from the TCGA database (https://portal.gdc.cancer.gov/). Thereafter, the tumor samples were divided into cold and hot tumors, based on the immune score of the tumor microenvironment. Moreover, the differentially expressed lncRNAs and miRNAs were obtained. Finally, the study jointly constructed a ceRNA network through differential analysis of the mRNA data for cold and hot tumors. The study first assessed the level of immune infiltration in the THCA tumor microenvironment then divided the samples into cold and hot tumors, based on the immune score. Additionally, a total of 568 up-regulated and 412 down-regulated DEGs were screened by analyzing the differences between hot and cold tumors. Thereafter, the study examined the differentially expressed genes for lncRNA and miRNA. The results revealed 629 differentially expressed genes related to lncRNA and 114 associated with miRNA. Finally, a ceRNA network of the differentially expressed genes was constructed. The results showed a five-miRNA hubnet, i.e., hsa-mir-204, hsa-mir-128, hsa-mir-214, hsa-mir-150 and hsa-mir-338. The present study identified the immune-related mRNA, lncRNA and miRNA in THCA then constructed a ceRNA network. These results are therefore important as they provide more insights on the immune mechanisms in THCA. The findings also provides additional information for possible THCA immunotherapy.

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“…Looking for tumor-related regulatory molecules and enrichment analysis of tumor-related molecules T cell-based cancer immunotherapy, such as checkpoint suppression or adoptive cell therapy, has greatly changed the way cancer is treated [39].We know that immunity plays a very important role in the occurrence and development of tumors. We rst calculated the differential genes between cancer and adjacent cancers, and then intersected the genes up-regulated in cold tumors (adjpvalue<0.05) with the highly expressed genes in the tumors.…”

Section: Enrichment Analysis Of Differential Genes and Construction Omentioning

confidence: 99%

Construction of ceRNA Network Based on TCGA and UCSC Xena Official Website to Provide Certain Help for Immunotherapy of Thyroid Cancer.

Qiu

et al. 2021

Preprint

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Background: Thyroid cancer is the most common endocrine tumor, and papillary thyroid carcinoma is the most common. Commonly used treatment methods include surgery and radiotherapy. As an emerging treatment option in recent years, immunotherapy has played an essential role in the treatment of many tumors, but there are few studies in thyroid cancer. Method: We first downloaded the mRNA and lncRNA data of thyroid cancer patients from the TCGA official website https://portal.gdc.cancer.gov/, and downloaded the miRNA of thyroid cancer patients from UCSC Xena https://xenabrowser.net/ data. Through the tumor microenvironment's immune score, tumor samples are divided into cold tumors and hot tumors. We obtained the differential genes of DEGs, lncRNA and miRNA, and jointly constructed a ceRNA network through differential analysis of the mRNA data of cold and hot tumours. Results: We first assessed the immune infiltration of the tumor microenvironment of patients with thyroid cancer, and divided the samples into cold tumors and hot tumors based on the immune score. A total of 568 up-regulated DEGs and 412 down-regulated DEGs were screened by analysing the difference between hot and cold tumours. Then we conducted a differential analysis of lncRNA and miRNA and obtained 629 differential genes of lncRNA, and 114 differential genes of miRNA. Finally, we constructed a ceRNA network for the acquired differential genes. Five miRNA-centric hubnets, hsa-mir-204, hsa-mir-128, hsa-mir-214, hsa-mir-150 and hsa-mir-338, have been identified. Conclusion: Our research has identified the immune-related mRNA, lncRNA and miRNA DEGs of thyroid cancer, and constructed a ceRNA network. This result is of great significance for exploring immune-related mechanisms of thyroid cancer and provides certain help for immunotherapy of thyroid cancer.

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Synergistic cancer immunotherapy combines MVA-CD40L induced innate and adaptive immunity with tumor targeting antibodies

Cited by 39 publications

References 67 publications

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

Evodiamine suppresses non-small cell lung cancer by elevating CD8+ T cells and downregulating the MUC1-C/PD-L1 axis

Identification of prognostic biomarkers related to the tumor microenvironment in thyroid carcinoma

Construction of ceRNA Network Based on TCGA and UCSC Xena Official Website to Provide Certain Help for Immunotherapy of Thyroid Cancer.

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