Vaccination with Antigen Combined with αβ-ATP as a Vaccine Adjuvant Enhances Antigen-Specific Antibody Production &lt;i&gt;via&lt;/i&gt; Dendritic Cell Activation

Matsuo, Keitaro; Nishiuma, Satoshi; Hasegawa, Yuta; Kawabata, Fumika; Kitahata, Kosuke; Nakayama, Takashi

doi:10.1248/bpb.b16-00087

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…Our understanding of the immunological characteristics of P2RY6 microenvironment makes us confident to infer that LUAD may affect tumor immunity and thus affect the prognosis of LUAD patients. Some genes of the same family with P2RY6 have developed corresponding immunotherapy [ 50 ]. Inspired by this, we think that P2RY6 may have a good prospect in the immune regulation of tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Immunological role and clinical prognostic significance of P2RY6 in lung adenocarcinoma: a multi-omics studies and single-cell sequencing analysis

Wu,

Dong

2023

World J Surg Onc

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Background There is increasing evidence that recombinant human P2Y purinoceptor 6 (P2RY6) may be involved in inflammatory responses. However, the role of P2RY6 in lung adenocarcinoma (LUAD) remains unknown. Methods We used transcriptomic, genomic, single-cell transcriptomic, and methylation sequencing data from The Cancer Genome Atlas database to analyze the aberrant status and prognostic value of P2RY6 in a variety of tumors. The LUAD single-cell sequencing dataset was used to explore the effect of P2RY6 on the tumor microenvironment. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to quantify immune cells in the tumor microenvironment. We also analyzed the correlation of P2RY6 with immune checkpoints and immune regulation-related genes. The correlation of between tumor mutation burden (TMB), microsatellite instability (MSI), and P2RY6 expression was also analyzed simultaneously. Tissue microarray and immunohistochemistry were employed to assess the expression of P2RY6 in internal tumor samples. Results Our findings indicate that P2RY6 exhibits significantly higher expression levels in various cancer tissues, particularly in LUAD. High expression of P2RY6 was closely associated with a poor prognosis for patients, and it plays a role in regulating immune-related pathways, such as cytokine-cytokine receptor interaction. Notably, P2RY6 expression is closely linked to the abundance of CD8 + T cells. Furthermore, we have developed a P2RY6-related inflammation prediction model that demonstrates promising results in predicting the prognosis of LUAD patients, with an AUC (area under the curve) value of 0.83. This performance is significantly better than the traditional TNM staging system. Through single-cell transcriptome sequencing analysis, we observed that high P2RY6 expression is associated with increased intercellular communication. Additionally, pathway enrichment analysis revealed that P2RY6 influences antigen presentation and processing pathways within the LUAD microenvironment. Conclusions This study suggests that P2RY6 would be a new target for immunotherapy in LUAD.

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Section: Discussionmentioning

confidence: 99%

Immunological role and clinical prognostic significance of P2RY6 in lung adenocarcinoma: a multi-omics studies and single-cell sequencing analysis

Wu,

Dong

2023

World J Surg Onc

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“…Our understanding of the immunological characteristics of P2RY6 microenvironment makes us con dent to infer that LUAD may affect tumor immunity and thus affect the prognosis of LUAD patients. Some genes of the same family with P2RY6 have developed corresponding immunotherapy [44] . Inspired by this, we think that P2RY6 may have a good prospect in the immune regulation of tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Immunological Role And Clinical Prognostic Significance of Risk Marker P2RY6 In Lung Adenocarcinoma

Hui

et al. 2021

Preprint

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There is increasing evidence that P2RY6 may be involved in inflammatory responses. However, the role of P2RY6 in a variety of cancers remains unknown. In this study, we comprehensively analyzed P2RY6 expression and its association with different types of malignancies using different multiple databases, and further explored the relationship between P2RY6 expression and prognosis in LUAD, and finally validated it using immunohistochemistry in LUAD. We found that P2RY6 was expressed at significantly higher levels in a variety of cancer tissues, and that poor patient prognosis was strongly associated with high P2RY6 expression. Further risk scoring revealed that P2RY6 is closely associated with the immune microenvironment of LUAD, which would suggest that P2RY6 would be a new target for immunotherapy in LUAD

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“…MF59 induces ATP release from cells at the injection site . Indeed, non‐hydrolysable ATP can act as a vaccine adjuvant, resulting in enhancement of antigen‐specific antibody responses . ATP may also activate Tregs and enhance their suppressive ability , although other studies showed that ATP can inhibit the suppressive ability and stability of Tregs .…”

Section: Discussionmentioning

confidence: 99%

A clinically applicable adjuvant for an atherosclerosis vaccine in mice

et al. 2018

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Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene-based oil-in-water adjuvant similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL-10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene-based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine.

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Vaccination with Antigen Combined with αβ-ATP as a Vaccine Adjuvant Enhances Antigen-Specific Antibody Production <i>via</i> Dendritic Cell Activation

Cited by 6 publications

References 24 publications

Immunological role and clinical prognostic significance of P2RY6 in lung adenocarcinoma: a multi-omics studies and single-cell sequencing analysis

Immunological role and clinical prognostic significance of P2RY6 in lung adenocarcinoma: a multi-omics studies and single-cell sequencing analysis

Immunological Role And Clinical Prognostic Significance of Risk Marker P2RY6 In Lung Adenocarcinoma

A clinically applicable adjuvant for an atherosclerosis vaccine in mice

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