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Journal of Reproductive Immunology Aug 2022The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for... (Review)
Review
The fallopian tubes (FT) play a key role in fertility by facilitating the movement of gametes to promote fertilisation and, subsequently, passage of the zygote for implantation. Histologically, the FT mucosa consists of three main cell types: secretory, ciliated and peg cells. In addition, several studies have reported the presence of immune cells. This systematic review aims to present a comprehensive analysis of the immune cell populations in the human FT, both in health and benign pathology, to promote a better understanding of tubal pathologies and their influence on infertility. A comprehensive literature search was conducted across five databases and augmented with manual citation chaining. Forty-two eligible studies were selected in accordance with PRISMA guidelines. Following screening, risk of bias assessments were conducted, data extracted and the findings presented thematically. T lymphocytes, predominantly CD8 T cells, represent the most abundant immune cell population within the healthy FT, with B lymphocytes, macrophages, NK cells and dendritic cells also localised to the tubal mucosa. There is evidence to suggest that lymphocyte and macrophage populations are susceptible to changes in the concentration of reproductive hormones. Tubal ectopic pregnancy, salpingitis, hydrosalpinx and endometriosis are all characterised by an increased population of macrophages in comparison to healthy FT. However, given the inconsistent evidence presented between studies, and the lack of studies examining all immune cell subtypes in tubal pathologies, only limited conclusions can be formulated on pathology-specific immune cell populations, and further research is required for validation.
Topics: CD8-Positive T-Lymphocytes; Fallopian Tubes; Female; Humans; Mucous Membrane; Pregnancy; Pregnancy, Tubal; Salpingitis
PubMed: 35644062
DOI: 10.1016/j.jri.2022.103646 -
Cancers May 2022Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25%... (Review)
Review
Bladder cancer is the ninth most common cancer worldwide. Over 75% of non-muscle invasive cancer patients require conservative local treatment, while the remaining 25% of patients undergo radical cystectomy or radiotherapy. Immune checkpoint inhibitors represent a novel class of immunotherapy drugs that restore natural antitumoral immune activity via the blockage of inhibitory receptors and ligands expressed on antigen-presenting cells, T lymphocytes and tumour cells. The use of immune checkpoint inhibitors in bladder cancer has been expanded from the neoadjuvant setting, i.e., after radical cystectomy, to the adjuvant setting, i.e., before the operative time or chemotherapy, in order to improve the overall survival and to reduce the morbidity and mortality of both the disease and its treatment. However, some patients do not respond to checkpoint inhibitors. As result, the capability for identifying patients that are eligible for this immunotherapy represent one of the efforts of ongoing studies. The aim of this systematic review is to summarize the most recent evidence regarding the use of immune checkpoint inhibitors, in a neoadjuvant and adjuvant setting, in the treatment of muscle-invasive bladder cancer.
PubMed: 35626149
DOI: 10.3390/cancers14102545 -
Frontiers in Molecular Biosciences 2022Immunoglobulin E (IgE)-mediated allergies are increasing in prevalence, with IgE-mediated food allergies currently affecting up to 10% of children and 6% of adults...
Immunoglobulin E (IgE)-mediated allergies are increasing in prevalence, with IgE-mediated food allergies currently affecting up to 10% of children and 6% of adults worldwide. The mechanisms underpinning the first phase of IgE-mediated allergy, allergic sensitization, are still not clear. Recently, the potential involvement of lipids in allergic sensitization has been proposed, with reports that they can bind allergenic proteins and act on immune cells to skew to a T helper type 2 (Th2) response. The objective of this systematic review is to determine if there is strong evidence for the role of lipids in allergic sensitization. Nineteen studies were reviewed, ten of which were relevant to lipids in allergic sensitization to food allergens, nine relevant to lipids in aeroallergen sensitization. The results provide strong evidence for the role of lipids in allergies. Intrinsic lipids from allergen sources can interact with allergenic proteins to predominantly enhance but also inhibit allergic sensitization through various mechanisms. Proposed mechanisms included reducing the gastrointestinal degradation of allergenic proteins by altering protein structure, reducing dendritic cell (DC) uptake of allergenic proteins to reduce immune tolerance, regulating Th2 cytokines, activating invariant natural killer T (iNKT) cells through CD1d presentation, and directly acting upon toll-like receptors (TLRs), epithelial cells, keratinocytes, and DCs. The current literature suggests intrinsic lipids are key influencers of allergic sensitization. Further research utilising human relevant models and clinical studies are needed to give a reliable account of the role of lipids in allergic sensitization.
PubMed: 35495627
DOI: 10.3389/fmolb.2022.832330 -
International Journal of Molecular... Feb 2022Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed... (Review)
Review
Glioblastoma (GBM) is the most common and malignant tumour of the central nervous system. Recent appreciation of the heterogeneity amongst these tumours not only changed the WHO classification approach, but also created the need for developing novel and personalised therapies. This systematic review aims to highlight recent advancements in understanding the molecular pathogenesis of the GBM and discuss related novel treatment targets. A systematic search of the literature in the PubMed library was performed following the PRISMA guidelines for molecular pathogenesis and therapeutic advances. Original and meta-analyses studies from the last ten years were reviewed using pre-determined search terms. The results included articles relevant to GBM development focusing on the aberrancy in cell signaling pathways and intracellular events. Theragnostic targets and vaccination to treat GBM were also explored. The molecular pathophysiology of GBM is complex. Our systematic review suggests targeting therapy at the stemness, p53 mediated pathways and immune modulation. Exciting novel immune therapy involving dendritic cell vaccines, B-cell vaccines and viral vectors may be the future of treating GBM.
Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Signal Transduction
PubMed: 35269752
DOI: 10.3390/ijms23052607 -
Current Oncology (Toronto, Ont.) Feb 2022Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients' long-term survival. This meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients' long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials.
METHODS
The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: "glioblastoma multiforme", "dendritic cell", "vaccination", "immunotherapy", "immune system", "immune response", "chemotherapy", "recurrence", and "temozolomide". Among the 157 screened, only 15 articles were eligible for the final analysis.
RESULTS
Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822-2.335, = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882-2.248, = 0.754). In contrast, DCV led to significantly longer 1-year OS (HR = 1.936, 95% CI: 1.396-2.85, = 0.001) and longer 2-year OS (HR = 3.670, 95% CI: 2.291-5.879, = 0.001) versus control groups. Hence, introducing DCV could lead to increased 1 and 2-year survival of patients by 1.9 and 3.6 times, respectively.
CONCLUSION
Antitumor regimens including DCV can effectively improve mid-term survival in patients suffering glioblastoma multiforme (GBM), but its impact emerges only after one year from vaccination. These data indicate the need for more time to achieve an anti-GBM immune response and suggest additional therapeutics, such as checkpoint inhibitors, to empower an earlier DCV action in patients affected by a very poor prognosis.
Topics: Brain Neoplasms; Dendritic Cells; Glioblastoma; Humans; Immunotherapy; Vaccination
PubMed: 35200574
DOI: 10.3390/curroncol29020075 -
Cells Dec 2021Chemical allergies are T cell-mediated diseases that often manifest in the skin as allergic contact dermatitis (ACD). To prevent ACD on a public health scale and avoid...
BACKGROUND
Chemical allergies are T cell-mediated diseases that often manifest in the skin as allergic contact dermatitis (ACD). To prevent ACD on a public health scale and avoid elicitation reactions at the individual patient level, predictive and diagnostic tests, respectively, are indispensable. Currently, there is no validated in vitro T cell assay available. The main bottlenecks concern the inefficient generation of T cell epitopes and the detection of rare antigen-specific T cells.
METHODS
Here, we systematically review original experimental research papers describing T cell activation to chemical skin sensitizers. We focus our search on studies published in the PubMed and Scopus databases on non-metallic allergens in the last 20 years.
RESULTS
We identified 37 papers, among them 32 (86%) describing antigen-specific human T cell activation to 31 different chemical allergens. The remaining studies measured the general effects of chemical allergens on T cell function (five studies, 14%). Most antigen-specific studies used peripheral blood mononuclear cells (PBMC) as antigen-presenting cells (APC, 75%) and interrogated the blood T cell pool (91%). Depending on the individual chemical properties, T cell epitopes were generated either by direct administration into the culture medium (72%), separate modification of autologous APC (29%) or by use of hapten-modified model proteins (13%). Read-outs were mainly based on proliferation (91%), often combined with cytokine secretion (53%). The analysis of T cell clones offers additional opportunities to elucidate the mechanisms of epitope formation and cross-reactivity (13%). The best researched allergen was -phenylenediamine (PPD, 12 studies, 38%). For this and some other allergens, stronger immune responses were observed in some allergic patients (15/31 chemicals, 48%), illustrating the in vivo relevance of the identified T cells while detection limits remain challenging in many cases.
INTERPRETATION
Our results illustrate current hardships and possible solutions to monitoring T cell responses to individual chemical skin sensitizers. The provided data can guide the further development of T cell assays to unfold their full predictive and diagnostic potential, including cross-reactivity assessments.
Topics: Allergens; Antigens; Epitopes, T-Lymphocyte; Humans; Lymphocyte Activation; Receptors, Antigen, T-Cell; Skin; T-Lymphocytes
PubMed: 35011644
DOI: 10.3390/cells11010083 -
Journal of Personalized Medicine Dec 2021Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test for tumor... (Review)
Review
Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test for tumor evolution and response to treatment through the analysis of circulating tumor cells (CTCs) and exosomes. We performed a systematic literature review (PRISMA guidelines) to describe the current knowledge about PD-L1 expression in liquid biopsies of PC patients: 101/159 (64%) cases revealed a variable number of PD-L1+ CTCs. Outcome correlations should be investigated in larger series. Nuclear PD-L1 expression by CTCs was occasionally associated with worse prognosis. Treatment (abiraterone, enzalutamide, radiotherapy, checkpoint-inhibitors) influenced PD-L1+ CTC levels. Discordance in PD-L1 status was detected between primary vs. metastatic PC tissue biopsies and CTCs vs. corresponding tumor tissues. PD-L1 is also released by PC cells through soluble exosomes, which could inhibit the T cell function, causing immune evasion. PD-L1+ PC-CTC monitoring and genomic profiling may better characterize the ongoing aggressive PC forms compared to PD-L1 evaluation on primary tumor biopsies/prostatectomy specimens (sometimes sampled a long time before recurrence/progression). Myeloid-derived suppressor cells and dendritic cells (DCs), which may have immune-suppressive effects in tumor microenvironment, have been found in PC patients circulation, sometimes expressing PD-L1. Occasionally, their levels correlated to clinical outcome. Enzalutamide-progressing castration-resistant PC patients revealed increased PD-1+ T cells and circulating PD-L1/2+ DCs.
PubMed: 34945784
DOI: 10.3390/jpm11121312 -
Frontiers in Immunology 2021Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and...
Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and chemoprevention remain the main risk-reducing modalities for those with hereditary cancer syndromes, as well as high-risk non-hereditary breast lesions such as ADH, ALH, or LCIS. Ductal carcinoma (DCIS) is a preinvasive malignant lesion of the breast that closely mirrors IBC and, if left untreated, develops into IBC in up to 50% of lesions. Certain high-risk patients with DCIS may have a 25% risk of developing recurrent DCIS or IBC, even after surgical resection. The development of breast cancer elicits a strong immune response, which brings to prominence the numerous advantages associated with immune-based cancer prevention over drug-based chemoprevention, supported by the success of dendritic cell vaccines targeting HER2-expressing BC. Vaccination against BC to prevent or interrupt the process of BC development remains elusive but is a viable option. Vaccination to intercept preinvasive or premalignant breast conditions may be possible by interrupting the expression pattern of various oncodrivers. Growth factors may also function as potential immune targets to prevent breast cancer progression. Furthermore, neoantigens also serve as effective targets for interception by virtue of strong immunogenicity. It is noteworthy that the immune response also needs to be strong enough to result in target lesion elimination to avoid immunoediting as it may occur in IBC arising from DCIS. Overall, if the issue of vaccine targets can be solved by interrupting premalignant lesions, there is a potential to prevent the development of IBC.
Topics: Animals; Antigens, Neoplasm; Breast Carcinoma In Situ; Breast Neoplasms; Cancer Vaccines; Carcinoma, Intraductal, Noninfiltrating; Disease Progression; Female; Humans; Neoplasm Invasiveness; Precancerous Conditions; Tumor Microenvironment; Vaccination
PubMed: 34899753
DOI: 10.3389/fimmu.2021.786286 -
The Cochrane Database of Systematic... Dec 2021Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 80% to 85% of all cases. For people with localised NSCLC (stages I to... (Review)
Review
BACKGROUND
Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 80% to 85% of all cases. For people with localised NSCLC (stages I to III), it has been speculated that immunotherapy may be helpful for reducing postoperative recurrence rates, or improving the clinical outcomes of current treatment for unresectable tumours. This is an update of a Cochrane Review first published in 2017 and it includes two new randomised controlled trials (RCTs).
OBJECTIVES
To assess the effectiveness and safety of immunotherapy (excluding checkpoint inhibitors) among people with localised NSCLC of stages I to III who received curative intent of radiotherapy or surgery.
SEARCH METHODS
We searched the following databases (from inception to 19 May 2021): CENTRAL, MEDLINE, Embase, CINAHL, and five trial registers. We also searched conference proceedings and reference lists of included trials.
SELECTION CRITERIA
We included RCTs conducted in adults (≥ 18 years) diagnosed with NSCLC stage I to III after surgical resection, and those with unresectable locally advanced stage III NSCLC receiving radiotherapy with curative intent. We included participants who underwent primary surgical treatment, postoperative radiotherapy or chemoradiotherapy if the same strategy was provided for both intervention and control groups.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected eligible trials, assessed risk of bias, and extracted data. We used survival analysis to pool time-to-event data, using hazard ratios (HRs). We used risk ratios (RRs) for dichotomous data, and mean differences (MDs) for continuous data, with 95% confidence intervals (CIs). Due to clinical heterogeneity (immunotherapeutic agents with different underlying mechanisms), we combined data by applying random-effects models.
MAIN RESULTS
We included 11 RCTs involving 5128 participants (this included 2 new trials with 188 participants since the last search dated 20 January 2017). Participants who underwent surgical resection or received curative radiotherapy were randomised to either an immunotherapy group or a control group. The immunological interventions were active immunotherapy Bacillus Calmette-Guérin (BCG) adoptive cell transfer (i.e. transfer factor (TF), tumour-infiltrating lymphocytes (TIL), dendritic cell/cytokine-induced killer (DC/CIK), antigen-specific cancer vaccines (melanoma-associated antigen 3 (MAGE-A3) and L-BLP25), and targeted natural killer (NK) cells. Seven trials were at high risk of bias for at least one of the risk of bias domains. Three trials were at low risk of bias across all domains and one small trial was at unclear risk of bias as it provided insufficient information. We included data from nine of the 11 trials in the meta-analyses involving 4863 participants. There was no evidence of a difference between the immunotherapy agents and the controls on any of the following outcomes: overall survival (HR 0.94, 95% CI 0.84 to 1.05; P = 0.27; 4 trials, 3848 participants; high-quality evidence), progression-free survival (HR 0.94, 95% CI 0.86 to 1.03; P = 0.19; moderate-quality evidence), adverse events (RR 1.12, 95% CI 0.97 to 1.28; P = 0.11; 4 trials, 4126 evaluated participants; low-quality evidence), and severe adverse events (RR 1.14, 95% CI 0.92 to 1.40; 6 trials, 4546 evaluated participants; low-quality evidence). Survival rates at different time points showed no evidence of a difference between immunotherapy agents and the controls. Survival rate at 1-year follow-up (RR 1.02, 95% CI 0.96 to 1.08; I = 57%; 7 trials, 4420 participants; low-quality evidence), 2-year follow-up (RR 1.02, 95% CI 0.93 to 1.12; 7 trials, 4420 participants; moderate-quality evidence), 3-year follow-up (RR 0.99, 95% CI 0.90 to 1.09; 7 trials, 4420 participants; I = 22%; moderate-quality evidence) and at 5-year follow-up (RR 0.98, 95% CI 0.86 to 1.12; I = 0%; 7 trials, 4389 participants; moderate-quality evidence). Only one trial reported overall response rates. Two trials provided health-related quality of life results with contradicting results. AUTHORS' CONCLUSIONS: Based on this updated review, the current literature does not provide evidence that suggests a survival benefit from adding immunotherapy (excluding checkpoint inhibitors) to conventional curative surgery or radiotherapy, for people with localised NSCLC (stages I to III). Several ongoing trials with immune checkpoints inhibitors (PD-1/PD-L1) might bring new insights into the role of immunotherapy for people with stages I to III NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Humans; Immunotherapy; Lung Neoplasms; Progression-Free Survival; Randomized Controlled Trials as Topic
PubMed: 34870327
DOI: 10.1002/14651858.CD011300.pub3 -
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