Crosstalk between ILC3s and Microbiota: Implications for Colon Cancer Development and Treatment with Immune Check Point Inhibitors.

Type 3 innate lymphoid cells (ILC3s) are primarily tissue-resident cells strategically localized at the intestinal barrier that exhibit the fast-acting responsiveness of classic innate immune cells. Populations of these lymphocytes depend on the transcription factor RAR-related orphan receptor and play a key role in maintaining intestinal homeostasis, keeping host-microbial mutualism in check. Current evidence has indicated a bidirectional relationship between microbiota and ILC3s. While ILC3 function and maintenance in the gut are influenced by commensal microbiota, ILC3s themselves can control immune responses to intestinal microbiota by providing host defense against extracellular bacteria, helping to maintain a diverse microbiota and inducing immune tolerance for commensal bacteria. Thus, ILC3s have been linked to host-microbiota interactions and the loss of their normal activity promotes dysbiosis, chronic inflammation and colon cancer. Furthermore, recent evidence has suggested that a healthy dialog between ILC3s and gut microbes is necessary to support antitumor immunity and response to immune checkpoint inhibitor (ICI) therapy. In this review, we summarize the functional interactions occurring between microbiota and ILC3s in homeostasis, providing an overview of the molecular mechanisms orchestrating these interactions. We focus on how alterations in this interplay promote gut inflammation, colorectal cancer and resistance to therapies with immune check point inhibitors.

Potential predictive role of gut microbiota to immunotherapy in HCC patients: a brief review.

The recent evolution of immunotherapy has revolutionised the treatment of hepatocellular carcinoma (HCC) and has led to new therapeutic standards. The advances in immunotherapy have been accompanied by the recognition of the role of the gut-liver axis in the progression of HCC but also of the clinical relevance of the gut microbiota, which influences host homeostasis but also cancer development and the response to treatment. Dysbiosis, by altering the tumour microenvironment, favours the activation of intracellular signalling pathways and promotes carcinogenesis. The gut microbiota, through their composition and immunomodulatory role, are thus strong predictors of the response to immune checkpoint inhibitor (ICI) treatment as well as an available target to improve ICI efficacy and reduce drug toxicities. In this review we examine the novel role of the gut microbiota as biomarkers in both the diagnosis of HCC and the clinical response to immunotherapy as well as its potential impact on clinical practice in the future.

Grapevine vitivirus A eradication in Vitis vinifera explants by antiviral drugs and thermotherapy.

Grapevine shoot cultures infected by Grapevine vitivirus A (GVA) were grown on Quorin-Lepoivre basic medium and submitted to in vitro chemotherapy and thermotherapy sanitation techniques. Ribavirin (Rb) at 20gml(-1), dihydroxypropyladenine (DHPA) at 60gml(-1) and their combination (RbDH) were added to the proliferating medium for three subsequent subcultures of 30 days each. Phytotoxicity was observed on drug-treated plantlets, which displayed a high percentage of mortality for each drug at doses higher than those aforementioned. Sequential ELISA were performed at the end of each subculture and ELISA-negative explants were submitted to RT-PCR. ELISA showed no antiviral activity following DHPA administration. Rb and RbDH treatment produced ELISA-negative explants which were assayed by RT-PCR and nested PCR. Biomolecular results showed no virus eradication in Rb treated explants but RbDH administration generated a percentage (40.0%) of GVA-free plantlets that permitted restoration of a new healthy generation of explants. Sixty percent (60%) of GVA eradication as confirmed by RT-PCR was obtained by in vitro thermotherapy at 36 degrees C for 57 days.

Attitudes of women of advanced maternal age undergoing invasive prenatal diagnosis and the impact of genetic counselling.

Despite the increasing availability and effectiveness of non-invasive screening for foetal aneuploidies, most women of advanced maternal age (AMA) still opt for invasive tests. A retrospective cross-sectional survey was performed on women of AMA undergoing prenatal invasive procedures, in order to explore their motivations and the outcome of preliminary genetic counselling according to the approach (individual or group) adopted. Of 687 eligible women, 221 (32.2%) participated: 117 had received individual counselling, while 104 had attended group sessions. The two groups did not differ by socio-demographic features. The commonest reported reason to undergo invasive tests was AMA itself (67.4%), while only 10.4% of women mentioned the opportunity of making informed choices. The majority perceived as clear and helpful the information received at counselling, and only 12.7% had doubts left that, however, often concerned non-pertinent issues. The impact of counselling on risk perception and decisions was limited: a minority stated their perceived risk of foetal abnormalities had either increased (6.8%) or reduced (3.6%), and only one eventually declined invasive test. The 52.6% of women expressed a preference toward individual counselling, which also had a stronger impact on perceived risk reduction (P=0.003). Nevertheless, group counselling had a more favourable impact on both clarity of understanding and helpfulness (P=0.0497 and P=0.035, respectively). The idea that AMA represents an absolute indication for invasive tests appears deeply rooted; promotion of non-invasive techniques may require extensive educational efforts targeted to both the general population and health professionals.