Search

Injectable hydrogels for cancer immunotherapy are effective for both active and passive approaches. Tumor‐infiltrating lymphocyte (TIL) immunoshaping can change the tumor microenvironment to favor tumor cell elimination. The primary objective of immunoshaping is to reduce regulatory T‐cells (Tregs), which can enhance the effectiveness of ex vivo immune cell therapy in solid tumors. A shear‐thinning injectable hydrogel that consists of gelatin and Laponite (Gel‐Lap) is used in this study. By optimizing the formulation, their immunotherapeutic and anti‐tumor properties are examined. Gemcitabine (GEM), an anti‐metabolite cancer chemotherapy agent, is loaded into a Gel‐Lap hydrogel (immunogel). The study compares the effects of immunogel on 4T1 inoculated breast cancer animal models. Results show that immunogel increases survival rates and significantly inhibits metastasis. The Treg cell population reduction is observed up to 70% in TILs and splenocyte population in line with CD8+ T‐cells population increment in inguinal lymph nodes near the tumor region; the CD8+ T‐cells function may be mediated through overexpression of eomesodermin (EOMES) as cytotoxic T lymphocyte (CTL) activation transcription factor. The human 3D cell culture model confirmed results in animal data demonstrating T‐cell migration through the hydrogel and anticancer efficacy. Local delivery of GEM using our silicate‐based hydrogel holds promise for editing tumor microenvironment in favor of systemic immune responses. [ABSTRACT FROM AUTHOR]

Dysbiosis of the vaginal microbiome poses a serious risk for sexual human immunodeficiency virus type 1 (HIV-1) transmission. Prevotella spp are abundant during vaginal dysbiosis and associated with enhanced HIV-1 susceptibility; however, underlying mechanisms remain unclear. Here, we investigated the direct effect of vaginal bacteria on HIV-1 susceptibility of vaginal CD4+ T cells. Notably, pre-exposure to Prevotella timonensis enhanced HIV-1 uptake by vaginal T cells, leading to increased viral fusion and enhanced virus production. Pre-exposure to antiretroviral inhibitors abolished P timonensis –enhanced infection. Our study shows that the vaginal microbiome directly affects mucosal CD4+ T-cell susceptibility, emphasizing importance of vaginal dysbiosis diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Introduction: The significant rise in incidence of Hepatitis C virus (HCV) infection among men-who-have-sex-with-men (MSM) living with HIV-1 suggests that HCV under specific circumstances is transmitted via sexual contact. During sexual transmission HCV has to cross the epithelial barrier to either directly enter the blood stream or indirectly via mucosal immune cells. However, the mechanisms of sexual transmission of HCV remain unclear. We investigated the role of Langerhans cells (LCs) in HCV susceptibility during sexual contact as LCs are among the first cells in mucosal tissues to encounter invading viruses. Methods: We investigated the phenotype of primary LCs in anal biopsies from MSM living with HIV-1. To investigate the role of primary LCs in HCV infection and transmission, we have used both isolated primary skin LCs and the ex vivo tissue transmission model. Results: Our data identified an important role for mucosal LCs in facilitating HCV transmission after HIV-1 exposure or immune activation. LCs were detected within mucosal anal tissues obtained from HIV-1 positive MSM biopsies. In order to perform functional studies, we used primary LCs from skin, which have a similar phenotype as mucosal LCs. Immature LCs were neither infected nor transmitted HCV to hepatocytes. Notably, exposure to HIV-1 significantly increased HCV transmission by LCs in the ex vivo transmission model. HIV-1 replication was crucial for the increased HCV transmission as HIV-1 inhibitors significantly reduced HIV-1-induced HCV transmission. Moreover, tissue immune activation of LCs also increased HCV transmission to target cells. Conclusions: Thus, our data strongly indicate that HIV-1 or immune activation in MSM leads to capture of HCV by mucosal LCs, which might facilitate transmission to other cells or allow entry of HCV into the blood. This novel transmission mechanism by LCs also implicates that the activation state of LCs is an important cellular determinant for HCV susceptibility after sexual contact. Keywords: HIV-1; Langerhans Cells; Hepatitis C virus; Immune activation; Viral transmission; Men-who-have-Sex-with-Men, 1 | INTRODUCTION Globally, 115 million people are infected with Hepatitis C virus (HCV) whereas 37 million people are infected with HIV-1, and approximately two million infected with both HIV-1 [...]

Human TRIM5[alpha] restricts HIV-1 infection of Langerhans cells through Langerin-dependent autophagy pathway. C-type lectin receptor-mediated anti-HIV activity Teunis Geijtenbeek and colleagues find a role for human E3-ubiquitin ligase tri-partite-containing motif 5[alpha] (TRIM5[alpha]) in restricting HIV-1 infection in Langerhans cells, a subset of dendritic cells present at the mucosal barrier. They show that capture of HIV-1 by the C-type lectin receptor Langerin serves to route the virus to a TRIM5[alpha]- and Langerin-dependent autophagy pathway. This mechanism of TRIM5[alpha]-mediated restriction differs from the proteasome-dependent mechanism by which rhesus TRIM5[alpha] is thought to restrict HIV-1, and seems to be a Langerhans-cell-specific restriction mechanism operating at the mucosal barrier. Langerhans cells are important in the defence against HIV-1 infection during sexual transmission, and this work highlights the potential of interventions involving C-type lectin receptors and autophagy-targeting strategies to promote cell-mediated resistance to HIV-1. The most prevalent route of HIV-1 infection is across mucosal tissues after sexual contact. Langerhans cells (LCs) belong to the subset of dendritic cells (DCs) that line the mucosal epithelia of vagina and foreskin and have the ability to sense and induce immunity to invading pathogens.sup.1. Anatomical and functional characteristics make LCs one of the primary targets of HIV-1 infection.sup.2. Notably, LCs form a protective barrier against HIV-1 infection and transmission.sup.3,4,5. LCs restrict HIV-1 infection through the capture of HIV-1 by the C-type lectin receptor Langerin and subsequent internalization into Birbeck granules.sup.5. However, the underlying molecular mechanism of HIV-1 restriction in LCs remains unknown. Here we show that human E3-ubiquitin ligase tri-partite-containing motif 5[alpha] (TRIM5[alpha]) potently restricts HIV-1 infection of LCs but not of subepithelial DC-SIGN.sup.+ DCs. HIV-1 restriction by TRIM5[alpha] was thus far considered to be reserved to non-human primate TRIM5[alpha] orthologues.sup.6,7,8,9, but our data strongly suggest that human TRIM5[alpha] is a cell-specific restriction factor dependent on C-type lectin receptor function. Our findings highlight the importance of HIV-1 binding to Langerin for the routeing of HIV-1 into the human TRIM5[alpha]-mediated restriction pathway. TRIM5[alpha] mediates the assembly of an autophagy-activating scaffold to Langerin, which targets HIV-1 for autophagic degradation and prevents infection of LCs. By contrast, HIV-1 binding to DC-SIGN.sup.+ DCs leads to disassociation of TRIM5[alpha] from DC-SIGN, which abrogates TRIM5[alpha] restriction. Thus, our data strongly suggest that restriction by human TRIM5[alpha] is controlled by C-type-lectin-receptor-dependent uptake of HIV-1, dictating protection or infection of human DC subsets. Therapeutic interventions that incorporate C-type lectin receptors and autophagy-targeting strategies could thus provide cell-mediated resistance to HIV-1 in humans., Author(s): Carla M. S. Ribeiro [sup.1] , Ramin Sarrami-Forooshani [sup.1] , Laurentia C. Setiawan [sup.1] , Esther M. Zijlstra-Willems [sup.1] , John L. van Hamme [sup.1] , Wikky Tigchelaar [sup.2] [...]

Considering HER2 as one of the well-known biomarkers in the cancer field, and published articles regarding serum levels of HER2, in this paper we tried to highlight the issue that most studies don’t stratify the HER-2 concentration of individuals in terms of gender. In this brief survey, healthy individuals with no prior non-communicable diseases were categorized as males (n=34) and females (n=43), and all samples were evaluated for plasma HER-2 levels at once. Surprisingly, the plasma level of HER-2 of healthy male individuals (mean= 2.28 ± 0.21 ng/mL) was significantly (P<0.0001) higher than the plasma level of HER-2 of healthy females (mean: 0.06 ± 0.09 ng/mL), with no overlap. Therefore, we suggest that more studies are required to re-check the cutoff values for HER-2 plasma levels based on gender since the clinical implications of a unique HER-2 cutoff for both genders may be seriously concerning. [ABSTRACT FROM AUTHOR]

Dysbiosis of the vaginal microbiome poses a serious risk for sexual human immunodeficiency virus type 1 (HIV-1) transmission. Prevotella spp are abundant during vaginal dysbiosis and associated with enhanced HIV-1 susceptibility; however, underlying mechanisms remain unclear. Here, we investigated the direct effect of vaginal bacteria on HIV-1 susceptibility of vaginal CD4+ T cells. Notably, pre-exposure to Prevotella timonensis enhanced HIV-1 uptake by vaginal T cells, leading to increased viral fusion and enhanced virus production. Pre-exposure to antiretroviral inhibitors abolished P timonensis-enhanced infection. Our study shows that the vaginal microbiome directly affects mucosal CD4+ T-cell susceptibility, emphasizing importance of vaginal dysbiosis diagnosis and treatment., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Candida albicans is an "opportunistic fungal agent" in cancer patients that can become colonized in both mucosal and deep tissues and cause severe infections. Most evidence has shown that C. albicans can enhance the progress of different cancers by several mechanisms such as generating virulence factors, participation in endogenous production of pro-inflammatory mediators, and stimulating a wide range of immune cells in the host. The main idea of this review is to describe a range of Candida -used mechanisms that are important in candidiasis-associated malignant processes and cancer development, particularly breast cancer. This review intends to provide a detailed discussion on different regulatory mechanisms of C. albicans that undoubtedly help to open new therapeutic horizons of cancer therapy in patients with fungal infection. The current therapeutic approach is not fully effective in immunocompromised and cancer patients, and further studies are required to find new products with effective antifungal properties and minimal side effects to increase the susceptibility of opportunistic fungal infections to conventional antifungal agents. So, in this situation, a special therapy should be considered to control the infection and simultaneously have the most therapeutic index on tumor patients., Competing Interests: None., (© 2024 mums.ac.ir All rights reserved.)