Previous studies have shown that cervical cancer cells only release low levels of pro-inflammatory cytokines owing to infection with human papillomaviruses. This results in low immunogenicity of the cancer cells. The viral dsRNA analog PolyIC has been suggested as a promising adjuvant for cervical cancer immunotherapy. However, little is known about the molecular requirements resulting in successful immune activation. Here, we demonstrate that stimulation of cervical cancer cells with PolyIC induced necroptotic cell death, which was strictly dependent on the expression of the receptor-interacting protein kinase RIPK3. Necroptotic cancer cells released interleukin-1α (IL-1α), which was required for powerful activation of dendritic cells (DC) to produce IL-12, a cytokine critical for anti-tumor responses. Again both, IL-1α release and DC activation, were strictly dependent on RIPK3 expression in the tumor cells. Of note, our in situ analyses revealed heterogeneous RIPK3 expression patterns in cervical squamous cell carcinomas and adenocarcinomas. In summary, our study identified a novel RIPK3-dependent mechanism that explains how PolyIC-treatment of cervical cancer cells leads to potent DC activation. Our findings suggest that the RIPK3 expression status in cervical cancer cells might critically influence the outcome of PolyIC-based immunotherapeutic approaches and should therefore be assessed prior to immunotherapy.
the aim of this study was to analyze the association of polymorphisms in alpha-ketoglutarate-dependent dioxygenase (FTO) and perilipin 2 (PLIN2) genes with carcass and meat quality traits in pigs reared in poland. the research covered 578 sows that belong to the following breeds: Duroc, Hampshire, Polish Landrace, Pietrain, Puławska and Polish Large White. FTO (fm244720:g.400c>g) and PLIN2 (gu461317:g.98g>A) genes variants were determined by means of pcr-rflp and Acrs-pcr methods respectively. Association between individual genotypes and analyzed traits was calculated by means of glm procedure for polish landrace, polish Large White and Puławska breeds separately and for all six breeds together in case of FTO gene. the results showed that FTO variants were associated with weight of loin without backfat and skin (WL), loin eye area (AL) and meat percentage (MP) in Polish Large White (P≤0.05), mean backfat thickness from 5 measurements (Bft) and ph measured 45 min after slaughter in m. longissimus dorsi (pH24 ld) as well as with water holding-capacity (WHC) in Puławska breed (P≤0.01). PLIN2 genotypes, however were correlated with WL and height of the loin eye (HL) in Polish Large White and Puławska (P≤0.05), AL in Polish Large White (P≤0.01) as well as luminosity (L*) in Puławska (P≤0.05) pigs. We observed most consistent relationships of PLIN2 snp with intramuscular fat content (IMF) and WHC. In 3 analyzed breeds GG genotype was connected with highest values of these traits (P≤0.05).
The dominant intrastromal T-cell infiltration in pancreatic cancer is mainly caused by the contact guidance through the excessive desmoplastic reaction and could represent one of the obstacles to an effective immune response in this tumor type. This study analyzed the collagen organization in normal and malignant pancreatic tissues as well as its influence on T-cell distribution in pancreatic cancer. Human pancreatic tissue was analyzed using immunofluorescence staining and multiphoton and SHG microscopy supported by multistep image processing. The influence of collagen alignment on activated T-cells was studied using 3D matrices and time-lapse microscopy. It was found that the stroma of malignant and normal pancreatic tissues was characterized by complex individual organization. T-cells were heterogeneously distributed in pancreatic cancer and there was no relationship between T-cell distribution and collagen organization. There was a difference in the angular orientation of collagen alignment in the peritumoral and tumor-cell-distant stroma regions in the pancreatic ductal adenocarcinoma tissue, but there was no correlation in the T-cell densities between these regions. The grade of collagen alignment did not influence the directionality of T-cell migration in the 3D collagen matrix. It can be concluded that differences in collagen organization do not change the spatial orientation of T-cell migration or influence stromal T-cell distribution in human pancreatic cancer. The results of the present study do not support the rationale of remodeling of stroma collagen organization for improvement of T-cell–tumor cell contact in pancreatic ductal adenocarcinoma.
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