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The natural adjuvant properties of bacterial ghosts (BGs) lie within the presence of intact pathogen-associated molecular patterns on their surface. BGs can improve the direct delivery, natural processing and presentation of target antigens within dendritic cells (DCs). Moreover, sensitization of human DCs by cancer cell lysate (oncolysate)-loaded BGs in the presence of IFN-α and GM-CSF enhanced DC maturation as indicated by an increased expression of maturation markers and co-stimulatory molecules, higher production of IL-12p70 and stimulation of significantly increased proliferation of both autologous CD4 and CD8 T cells compared to DCs matured in the presence of purified lipopolysaccharide. The induced T cells efficiently recognized oncolysate-derived tumor-associated antigens expressed by cancer cells used for the production of oncolysate. Our optimized one-step simultaneous antigen delivery and DC maturation-inducing method emerges as a promising tool for the development and implementation of next-generation cellular cancer immunotherapies.

The evaluation of carbon-based nanomaterials’ (C-BNMs’) interactions with the immune system, notably their ability to cause inflammation, is a critical step in C-BNM health risk assessment. Particular attention should be given to those C-BNMs that do not cause direct cytotoxicity or inflammation on their own. However, the intracellular presence of these non-biodegradable nanomaterials could dysregulate additional cell functions. This is even more crucial in the case of phagocytes, which are the main mediators of defensive inflammation towards pathogens. Hence, our study was focused on multi-walled carbon nanotubes (MWCNTs) and two different types of graphene platelets (GPs) and whether their intracellular presence modulates a proinflammatory response from human primary monocytes towards common pathogens. Firstly, we confirmed that all tested C-BNMs caused neither direct cytotoxicity nor the release of tumour necrosis factor α (TNF-α), interleukin (IL)-6 or IL-10. However, such pre-exposed monocytes showed increased responsiveness to additional bacterial stimuli. In response to several types of bacteria, monocytes pre-treated with GP1 produced a significantly higher quantity of TNF-α, IL-6 and IL-10. Monocytes pre-treated with MWCNTs produced increased levels of IL-10. All the tested C-BNMs enhanced monocyte phagocytosis and accelerated their differentiation towards macrophages. This study confirms the immunomodulatory potential of C-BNMs.

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Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant isoform CD44v8-10. Our aim is to show that upregulation of CD44v8-10 isoform is a possible marker of precancerous lesion in human colon.Methods: We analysed pairs of fresh biopsy specimen of large intestine in a cohort of 50 patients. We studied and compared alternative splicing profile of CD44 gene in colon polyps and adjoined healthy colon mucosa. We performed end-point and qRT PCR, western blotting, IHC staining and flow cytometry analyses.Results: We detected more than five-fold overexpression of CD44v8-10 isoform and almost twenty-fold downregulation of standard isoform CD44s in colon polyps compared to adjoined healthy tissue with p = 0.018 and p < 0.001 in a cohort of 50 patients. Our results also show that aberrant splicing of CD44 occurs in both biologically distinct subtypes of colorectal adenoma possibly in ESRP-1 specific manner.Conclusion: 92% of the colon polyp positive patients overexpressed CD44v8-10 isoform in their colon polyps while only 36% of them had positive fecal occult blood test which is currently a standard non-invasive screening technique.Impact: We believe that our results are important for further steps leading to application of CD44v8-10 isoform as a biomarker of colorectal precancerosis in non-invasive detection. Early detection of colon precancerosis means successful prevention of colorectal carcinoma.

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