The role of microbiota and immune system crosstalk in cancer development and therapy

Cancer is a multifactorial disease that is the second leading cause of death after cardiovascular disease in the world. In recent years, microbiota's role in the regulation and homeostasis of the immune system has been considered. Moreover, the immune system can affect the microbiota content. These interactions are critical to the functioning of the immune system. Numerous studies in animal and human models have shown the association of changes in microbiota components with the formation of an inhibitory microenvironment in the tumor and its escape from the immune system. Microbiota also plays a crucial role in the success of various anti-tumor treatments, and its modification leads to success in cancer treatment. The success of anti-tumor therapies that directly target the immune system, such as immune checkpoint blockade and T cell therapy, is also affected by the patient's microbiota composition. It seems that in addition to examining the patient's genetics, precision medicine should pay attention to the patient's microbiota in choosing the appropriate treatment method, and together with usual anti-tumor therapies, microbiota may be modified. This review discusses various aspects of the relationship between microbiota and anti-tumor immunity and its successful treatment

Impact of gut microbiota on immune system

The commensal microflora collection known as microbiota has an essential role in maintaining the host's physiological homeostasis. The microbiota has a vital role in induction and regulation of local and systemic immune responses. On the other hand, the immune system involves maintaining microbiota compositions. Optimal microbiota-immune system cross-talk is essential for protective responses to pathogens and immune tolerance to self and harmless environmental antigens. Any change in this symbiotic relationship may cause susceptibility to diseases. The association of various cancers and autoimmune diseases with microbiota has been proven. Here we review the interaction of immune responses to gut microbiota, focusing on innate and adaptive immune system and disease susceptibility

Combinatorial delivery of antigen and TLR agonists via PLGA nanoparticles modulates Leishmania major-infected-macrophages activation

Appropriate activation of macrophages is critical for the elimination of Leishmania parasites, which resides in this cell. Some species of Leishmania (L.) fails to stimulate macrophages and establish a chronic infection. To overcome this suppression and induce an innate immune response, the effect of PLGA-encapsulated soluble antigens of Leishmania (SLA) along with agonists of TLR1/2 (Pam3CSK4) and TLR7/8 (R848) nanoparticles (NPs) on activation of L. major-infected-macrophages were investigated and were compared with those of soluble formulations. SLA and R848 were encapsulated into the PLGA, while Pam3CSK4 adsorbed onto the surface of nanoparticles. The kinetics of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and iNOS genes expression were investigated by qPCR over 72 h. The parasite load was also quantified by qPCR.The results indicated that engulfment of L. major promastigotes does not induce any pro-inflammatory cytokines expression by macrophages; however, the infected-cells are capable of responding to the TLRs agonists, and a lesser extent, to the SLA stimulation. Encapsulation resulted in increased strength of the IL-1β, IL-6, TNF-α, and increased and prolonged time of iNOS expression. Also, encapsulation showed the leishmanicidal activity by decreasing parasite load in treated NPs formulations. Among the different combinations of the components, the triple (SLA-R848-Pam3CSK4) forms promoted the highest activation of macrophages, followed by dual SLA-Pam3CSK4 and SLA-R848 NPs.In conclusion, the findings of this study indicate that the addition of SLA in combination with TLR1/2 and TLR7/8 agonists either in NPs or in soluble forms overcome the suppression of L. major-infected macrophages. Moreover, encapsulation increases the strength and duration of the cytokines and iNOS expression, in parallel with decreasing parasite load, suggesting a longer availability or delivery of the NPs into the macrophages. These findings highlight the advantages of particulate therapeutic vaccine formulations

Bacteroides Fragilis Supernatant Plays Anti-Viability Roles Accompanied by Apoptosis and Cell Cycle Arrest via P62/Caspase8/ Bax/Fas Pathway in Colorectal Adenocarcinoma Cell Line: Anticancer effects of B. fragilis

From two classes of Bacteroides fragilis, enterotoxigenic B. fragilis (ETBF) is associated with colorectal cancer (CRC), yet several non-toxigenic B. fragilis (NTBF) confers powerful health benefits to the host and may be potential probiotic. In this study, the HT-29 cell line was treated with the supernatant of NTBF strain ATCC-23745. Then, the expression level of mTOR /p62/Caspase8/Bax proposed signaling pathway and cell viability, cell apoptosis, and cell cycle progression were determined using Real-time PCR and flow cytometry, respectively. We found that the B. fragilis supernatant inhibited cell proliferation and increased cell apoptosis in a dose- and time-dependent manner. Further, the arrest of the HT-29 cells at the G1 and sub-G1 phases also signified apoptotic cell death after 24 and 72h. The gene expression study revealed that the supernatant significantly up-regulated the Caspase8/Bax/Fas-mediated apoptosis signaling while suppressing the anti-apoptotic mTOR and p62 expression. Our findings suggest that the NTBF ATCC-23745 strain may be a potential probiotic and can be used in CRC treatment

Comparative study of pathogenic and non-pathogenic Escherichia coli outer membrane vesicles and prediction of host-interactions with TLR signaling pathways

Abstract Objective The intestine is the major defensive barrier in the body by having more than 60% of the immune cells in the intestinal mucosa. The aim of this study was to evaluate the Toll like receptor (TLR) signaling pathways and immune response profiles, against outer membrane vesicles (OMVs) in pathogenic and non-pathogenic strains of Escherichia coli. Results Our results demonstrated that despite inducing inflammatory and regulatory responses to OMVs released by both strains, there is a remarkable difference in the nature and severity of these responses between the two strains. Following the production and release of OMV by the pathogenic strain, the expressions of the pro-inflammatory cytokines were significantly elevated, in comparison to the non-pathogenic strains. Eventually, our findings suggest that OMV released by the pathogen strain might be colonized, causing inflammation, eliminating the tight junctions of epithelial cells and damaging underlying cells, without the presence of IL-17 at the inflammation site. This could have happened to prevent the development of more severe inflammation, which could lead to the inhibition of colonization. The production of IL-10 is also preventing such inflammations. On the other hand, OMV released by non-pathogenic E. coli appears to influence intestinal homeostasis by causing more anti-inflammatory responses and mild inflammation

Isolation and characterization of anti c-met single chain fragment variable (scFv) antibodies

The receptor tyrosine kinase (RTK) Met is the cell surface receptor for hepatocyte growth factor (HGF) involved in invasive growth programs during embryogenesis and tumorgenesis. There is compelling evidence suggesting important roles for c-Met in colorectal cancer proliferation, migration, invasion, angiogenesis, and survival. Hence, a molecular inhibitor of an extracellular domain of c-Met receptor that blocks c-Met-cell surface interactions could be of great thera-peutic importance. In an attempt to develop molecular inhibitors of c-Met, single chain variable fragment (scFv) phage display libraries Tomlinson I + J against a specific synthetic oligopeptide from the extracellular domain of c-Met receptor were screened; selected scFv were then characterized using various immune techniques. Three c-Met specific scFv (ES1, ES2, and ES3) were selected following five rounds of panning procedures. The scFv showed specific binding to c-Met receptor, and significantly inhibited proliferation responses of a human colorectal carcinoma cell line (HCT-116). Moreover, anti- apoptotic effects of selected scFv antibodies on the HCT-116 cell line were also evaluated using Annexin V/PI assays. The results demonstrated rates of apoptotic cell death of 46.0, 25.5, and 37.8% among these cells were induced by use of ES1, ES2, and ES3, respectively. The results demonstrated ability to successfully isolate/char-acterize specific c-Met scFv that could ultimately have a great therapeutic potential in immuno-therapies against (colorectal) cancers

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Additional file 1. Expression analysis of TLRs and interleukins in Caco2 stimulation. Caco2 after 24 h stimulation with OMVs. Data are presented as fold-change compared to untreated control cells. Statistical differences were assessed by the t-test. ∗ p ≤ 0.05, versus control cells

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Additional file 2. Clustergram plot of genes involved in TLRs signalling pathways. In order to demonstrate a heat map dendrograms, showing the co-regulated genes, a clustergram for the entire dataset was mapped, using non-supervised hierarchical clustering