CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies

Bullock, Timothy N. J.

doi:10.1038/s41423-021-00734-4

Cited by 60 publications

(36 citation statements)

References 95 publications

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“…In order to further explore the guiding role of the model in the chemotherapy and immunotherapy of patients with different subtypes of gastric cancer, we analyzed the difference in the expression of the immune checkpoints and the sensitivity to general chemotherapy drugs in different groups. According to our results, most immune checkpoints are highly expressed in high-risk groups such as CD27, CD28, and CD40, indicating that immune checkpoint inhibitors may be more beneficial to high-risk groups for the up-regulation of immune checkpoint-related genes [ 60 , 61 , 62 ]. Meanwhile, we highlighted the fact that high-risk patients exhibited higher sensitivities to conventional chemotherapy drugs, such as Bryostatin.1, Cisplatin, Dasatinib, Docetaxel, Gemcitabine, Parthenolide, Pazopanib, Rapamycin, Sunitinib, Temsirolimus, and Vinblastine, the only exception being Mitomycin C. This conclusion is also largely consistent with clinical dosing habits, where surgery combined with radiotherapy is usually used for patients evaluated for poor prognosis [ 63 ].…”

Section: Discussionmentioning

confidence: 96%

Prognosis Risk Model Based on Pyroptosis-Related lncRNAs for Gastric Cancer

Jiang

Fang

2023

Biomolecules

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Gastric cancer (GC) is a malignant tumor with a low survival rate, high recurrence rate, and poor prognosis. With respect to this, pyroptosis is a type of programmed cell death that can affect the occurrence and development of tumors. Indeed, long non-coding RNAs (lncRNAs) were broadly applied for the purposes of early diagnosis, treatment, and prognostic analysis in regard to cancer. Based on the association of these three purposes, we developed a novel prognosis risk model based on pyroptosis-related lncRNAs (PRlncRNAs) for GC. The PRlncRNAs were obtained via univariate and multivariate Cox regression in order to build the predictive signatures. The Kaplan–Meier and gene set enrichment analysis (GSEA) methods were used to evaluate the overall survival (OS) and functional differences between the high- and low-risk groups. Moreover, the correlation of the signatures with immune cell infiltration was determined through single-sample gene set enrichment analysis (ssGSEA). Finally, we analyzed this correlation with the treatment responses in the GC patients; then, we performed quantitative reverse transcription polymerase chain reactions (qRT-PCRs) in order to verify the risk model. The high-risk group received a worse performance in terms of prognosis and OS when compared to the low-risk group. With respect to this, the area under the receiver operating characteristic curve (ROC) was found to be 0.808. Through conducting the GSEA, it was found that the high-risk groups possessed a significant enrichment in terms of tumor–immunity pathways. Furthermore, the ssGSEA revealed that the predictive features possessed strong associations with immune cell infiltration in regard to GC. In addition, we highlighted that anti-immune checkpoint therapy, combined with conventional chemotherapy drugs, may be more suitable for high-risk patients. The expression levels of LINC01315, AP003392.1, AP000695.2, and HAGLR were significantly different between the GC cell lines and the normal cell lines. As such, the six PRlncRNAs could be regarded as important prognostic biomarkers for the purposes of subsequent diagnoses, treatments, prognostic predictions, and the mechanism research of GC.

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Section: Discussionmentioning

confidence: 96%

Prognosis Risk Model Based on Pyroptosis-Related lncRNAs for Gastric Cancer

Jiang

Fang

2023

Biomolecules

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“…These results suggested that CD40 and CD40L might exert a distinct pathogenic role in the mechanisms of AD and AA. Since CD40/CD40L are essential components in both innate and acquired immunity, monoclonal antibodies targeting CD40/CD40L, either antagonistic or agonistic, have attracted widespread attention in the field of autoimmune diseases and cancers, respectively (Karnell et al, 2019;Bullock 2022). There were already randomized controlled trials supporting the therapeutic value of antagonistic anti-CD40 monoclonal antibodies in autoimmune diseases such as rheumatoid arthritis and graves hyperthyroidism (Espié et al, 2020;Kahaly et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Blocking the interaction between CD40/CD40L, using genetic or pharmacological (i.e., monoclonal antibody) means, has been implicated in various autoimmune diseases such as rheumatoid arthritis ( Karnell et al, 2019 ). On the opposite side, the stimulation of CD40 through agonistic antibodies has been regarded as a promising approach for cancer treatment ( Bullock 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Causal associations between CD40/CD40L and aortic diseases: A mendelian randomization study

Xiao

Xuan²,

Chen³

et al. 2022

Front. Genet.

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Background: CD40 and CD40L have been reported as associated with aortic dissection (AD) and aortic aneurysm (AA), but the causality of the associations has not been established yet.Methods: We conducted a two-sample Mendelian randomization (MR) study to assess the causal inference between CD40/CD40L and aortic diseases including AD and AA. The instrumental variables (IVs) for CD40 and CD40L were selected from a high-quality protein quantitative trait loci dataset released by a genomic study involving 30,931 individuals of European ancestry. The genome-wide association studies summary statistics for AD and AA were from the FinnGen Release 7, with 288638 controls for all outcomes of interests, 680 cases for AD and 6,092 cases for AA, also from European ancestry. For AA subtypes, there were 5,881 cases of thoracic AA (TAA) and 2,434 cases of abdominal AA (AAA) respectively. Inverse-variance weighted and Wald ratio were applied for calculating causal estimates. Horizontal pleiotropy and heterogeneity were assessed using MR-Egger regression analysis and Cochran Q test, respectively. Leave-one-out analyses were further performed.Results: Three single-nucleotide polymorphisms (SNPs) for CD40 and one SNP for CD40L were selected as IVs. We found genetic proxied CD40 levels inversely associated with the risk of AD (odds ratio [OR]: 0.777, 95% confidence interval [CI]: 0.618–0.978, p = 0.031) and AA (OR: 0.905, 95% CI: 0.837–0.978, p = 0.012), consistent across TAA (both p < 0.050). There were trends of increased risks of AD and AA in the presence of CD40L while not reaching statistical significance. No significant horizontal pleiotropy or heterogeneity was observed.Conclusion: Our MR study provides evidence supporting the causal association between CD40 and the reduced risks of both AD and AA.

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“…[85] So far, various receptors were utilized for DC-specific antigen cytosolic delivery (Figure 7a), such as Fcγ receptors (FcγRs), MHC class II molecules, CD40, and C-type lectin receptors (CLRs). [86] Efficient targeting not only requires high specificity for the receptor that is abundantly expressed on the surface of DCs but also the ability to be rapidly internalized and loaded into compartments that contain elements of the antigen-processing machinery. [85] Among CLRs, DEC-205 Figure 7.…”

Section: Active Targeting Of Ln-resident Apcsmentioning

confidence: 99%

Nanotechnology‐Assisted Immunoengineering for Cancer Vaccines

Mamuti

Chen

Jiang

2022

Advanced NanoBiomed Research

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Recently, approaches based on nano‐immunoengineering have been developed to optimize the potency of vaccines while minimizing toxicity. To achieve desirable immune responses, vaccines should be able to traffic into lymph nodes (LN) and provide antigen and inflammatory signals for a sufficient temporal duration, to activate the desired cellular and humoral immunity. In that case, the application of nanotechnology in vaccine design provides the possibility of co‐delivering of antigen and adjuvants to the targeted organs, tissues, cells, or even intracellular compartments at the determined time to optimize the qualities of immune responses. Herein, the recent advances on nanovaccine design, including a brief summary of natural and synthetic biomaterials for antigen and adjuvant packing, are reviewed. The emerging approaches for regulating pharmacokinetics of vaccines will be further discussed especially for LN targeting as well as antigen uptake by antigen‐presenting cells. Those advances provide a prospect of shaping immune response by immunoengineering‐based nanovaccines.

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CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies

Cited by 60 publications

References 95 publications

Prognosis Risk Model Based on Pyroptosis-Related lncRNAs for Gastric Cancer

Prognosis Risk Model Based on Pyroptosis-Related lncRNAs for Gastric Cancer

Causal associations between CD40/CD40L and aortic diseases: A mendelian randomization study

Nanotechnology‐Assisted Immunoengineering for Cancer Vaccines

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