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International Journal of Molecular... Nov 2021The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and...
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.
The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients' serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.
Topics: Animals; B7-H1 Antigen; Cell Line, Tumor; Cytokines; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Killer Cells, Natural; Male; Mice; Programmed Cell Death 1 Receptor; Prostatic Neoplasms; T-Lymphocytes, Cytotoxic; Tumor Escape; Tumor Microenvironment; Wnt Signaling Pathway
PubMed: 34830209
DOI: 10.3390/ijms222212330 -
Journal of the International AIDS... Aug 2019Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV...
INTRODUCTION
Hepatitis C virus (HCV) is a major public health threat. Although the recent availability of highly effective directly acting antivirals created optimism towards HCV elimination, there is ongoing transmission of HCV in men who have sex with men (MSM). We here report current epidemiological trends and synthesise evidence on behavioural, network, cellular and molecular host factors associated with sexual transmission of HCV, in particular the role of HIV-1 co-infection. We discuss prevention opportunities focusing on the potential of HCV treatment.
METHODS
We searched MEDLINE, fact sheets from health professional bodies and conference abstracts using appropriate keywords to identify and select relevant reports.
RESULTS AND DISCUSSION
Recent studies strongly suggest that HCV is transmitted via sexual contact in HIV-positive MSM and more recently in HIV-negative MSM eligible for or on pre-exposure prophylaxis. The reinfection risk following clearance is about 10 times the risk of primary infection. International connectedness of MSM transmission networks might contribute to ongoing reinfection. Some of these networks might overlap with networks of people who inject drugs. Although, the precise mechanisms facilitating sexual transmission remain unclear, damage to the mucosal barrier in the rectum could increase susceptibility. Mucosal dendritic cell subsets could increase HCV susceptibility by retaining HCV and transmitting the virus to other cells, allowing egress into blood and liver. Early identification of new HCV infections is important to prevent onward transmission, but early diagnosis of acute HCV infection and prompt treatment is hampered by the slow rate of HCV antibody seroconversion, which in rare cases may take more than a year. Novel tests such as testing for HCV core antigen might facilitate early diagnosis.
CONCLUSIONS
High-risk sexual behaviour, network characteristics, co-infection with sexually transmitted infections like HIV-1 and other concomitant bacterial and viral sexually transmitted infections are important factors that lead to HCV spread. Targeted and combined prevention efforts including effective behavioural interventions and scale-up of HCV testing and treatment are required to halt HCV transmission in MSM.
Topics: Coinfection; HIV Infections; HIV-1; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Male; Sexual and Gender Minorities; Sexually Transmitted Diseases
PubMed: 31468692
DOI: 10.1002/jia2.25348 -
International Journal of Molecular... Dec 2020Natural killer (NK) cells, as members of the innate immune system, and natural killer T (NKT) cells, bridging innate and adaptive immunity, play a prominent role in...
Natural killer (NK) cells, as members of the innate immune system, and natural killer T (NKT) cells, bridging innate and adaptive immunity, play a prominent role in chronic inflammatory diseases and cancerogenesis, yet have scarcely been examined in oral diseases. Therefore, systematic research on the latest literature focusing on NK/NKT cell-mediated mechanisms in periodontal disease, including the time period 1988-2020, was carried out in MEDLINE (PubMed) using a predetermined search strategy, with a final selection of 25 studies. The results showed that NK cells tend to have rather proinflammatory influences via cytokine production, cytotoxic effects, dendritic-cell-crosstalk, and autoimmune reactions, while contrarily, NKT cell-mediated mechanisms were proinflammatory and immunoregulatory, ranging from protective effects via B-cell-regulation, specific antibody production, and the suppression of autoimmunity to destructive effects via cytokine production, dendritic-cell-crosstalk, and T-/B-cell interactions. Since NK cells seem to have a proinflammatory role in periodontitis, further research should focus on the proinflammatory and immunoregulatory properties of NKT cells in order to create, in addition to antibacterial strategies in dental inflammatory disease, novel anti-inflammatory therapeutic approaches modulating host immunity towards dental health.
Topics: Animals; Humans; Immunity, Innate; Killer Cells, Natural; Natural Killer T-Cells; Periodontal Diseases
PubMed: 33371393
DOI: 10.3390/ijms21249766 -
Diagnostic Pathology Aug 2022Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm of mesenchymal origin. FDCS of gastrointestinal tract (GI) are exceedingly uncommon.
BACKGROUND
Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm of mesenchymal origin. FDCS of gastrointestinal tract (GI) are exceedingly uncommon.
CASE PRESENTATION
We report the first case of classic type FDCS in a 34-year-old male with Birt-Hogg-Dubé syndrome, which presented as a mass at the ileo-cecal junction. He received no further treatment after resection and remained disease free for 3.5 years. We further analyze and review the clinical and pathologic findings of 33 cases of GI tract FDCS reported in the literature.
CONCLUSIONS
There are two distinct subtypes of FDCS in the GI tract: the classic type occurs in relatively younger patients (mean = 45.3 years) without Epstein-Barr virus (EBV) association, and behaves more aggressively; the inflammatory subtype presents as colonic polypoid tumor in older patients (mean = 60.7 years) and is EBV positive. The clinical outcome in the latter group appears favorable although mortality rate is not necessarily low.
Topics: Adult; Aged; Humans; Male; Dendritic Cell Sarcoma, Follicular; Disease-Free Survival; Epstein-Barr Virus Infections; Gastrointestinal Tract; Herpesvirus 4, Human
PubMed: 35941667
DOI: 10.1186/s13000-022-01246-z