Pathogen-induced tissue-resident memory T17 (T17) cells amplify autoimmune kidney disease.

Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (T) cells persist in peripheral organs and provide immune protection against reinfection. However, whether T cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown.

Early Arterial Intimal Thickening and Plaque Is Related with Treatment Regime and Cardiovascular Disease Risk Factors in Young Adults Following Childhood Hematopoietic Stem Cell Transplantation.

The long-term vascular effects following childhood hematopoietic stem cell transplantation (HSCT) are not well characterized. We compared arterial wall morphology and function using very-high resolution ultrasound (25-55 MHz) in 62 patients following autologous ( = 19) or allogenic ( = 43) HSCT for childhood malignancies and hematological disease (median age 25.9 years, IQR 21.

The induction and function of the anti-inflammatory fate of T17 cells.

T17 cells exemplify environmental immune adaptation: they can acquire both a pathogenic and an anti-inflammatory fate. However, it is not known whether the anti-inflammatory fate is merely a vestigial trait, or whether it serves to preserve the integrity of the host tissues. Here we show that the capacity of T17 cells to acquire an anti-inflammatory fate is necessary to sustain immunological tolerance, yet it impairs immune protection against S.

Long-term renal prognosis and risk for hypertension after myeloablative therapies in survivors of childhood high-risk neuroblastoma: A nationwide study.

Background: Patients with high-risk neuroblastoma (HR NBL) treated with myeloablative regimens are reported to be at risk for cardiovascular morbidity, and this risk may be increased by impaired renal function.

Procedure: Long-term renal function was assessed in a national cohort of 18 (age 22.4 ± 4.

Male Gonadal Function after Allogeneic Hematopoietic Stem Cell Transplantation in Childhood: A Cross-Sectional, Population-Based Study.

Male gonadal dysfunction is a frequent late effect after pediatric hematopoietic stem cell transplantation (HSCT), but detailed insight into patterns of male gonadal function at long-term is limited by retrospective studies without semen sample data. In this study, we investigated the risk of azoospermia and testosterone deficiency, the diagnostic value of markers of spermatogenesis, and paternity at long-term follow-up after pediatric allogeneic HSCT. All male HSCT survivors age ≥18 years, transplanted in Denmark or Finland between 1980 and 2010, were invited to participate in this cross-sectional study.

Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume.

Background: After neoadjuvant chemotherapy of breast cancer pathologic complete response (pCR) indicates a favorable prognosis. Among non-selected patients, pCR is, however, achieved in only 10-30%. Early evaluation of tumour response to treatment would facilitate individualized therapy, with ineffective chemotherapy interrupted or changed.

The Bones of Children With Obesity.

Excess adiposity in childhood may affect bone development, ultimately leading to bone frailty. Previous reports showing an increased rate of extremity fractures in children with obesity support this fear. On the other hand, there is also evidence suggesting that bone mineral content is higher in obese children than in normal weight peers.

Inflammation-induced tissue damage mimicking GvHD in human skin models as test-platform for immunotherapeutics.

With cellular products being on the front run there is a rising demand for non-animal-based test platforms to predict, study and treat undesired immunity. Here, we generated human organotypic skin models from human biopsies isolating and expanding keratinocytes, fibroblasts and microvascular endothelial cells finally allowing to seed these components on a collagen matrix or a biological vascularized scaffold matrix in a bioreactor. Afterwards, we were able to induce inflammation-based tissue damage by pre-stimulated mismatched allogeneic lymphocytes and/or inflammatory cytokine containing supernatants histomorphologically mimicking severe graft versus host disease (GvHD) of the skin.

Systemic interleukin 10 levels indicate advanced stages while interleukin 17A levels correlate with reduced survival in esophageal adenocarcinomas.

Introduction: Reflux promotes esophageal adenocarcinomas (EAC) creating a chronic inflammatory environment. EAC show an increasing incidence in the Western World and median survival rates are still low. The main reasons for poor prognosis despite new multimodal therapies are diagnosis of EACs at an already advanced stage and distant metastases.

Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6B helper T cells in systemic lupus erythematosus.

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4CCR6IL-7RT cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6B helper T cells were phenotypically distinct from follicular helper T (T) cells and lacked BCL6 expression.

Sessile Serrated Polyps Without Dysplasia Thrives With Asymmetric Relocation of Cell Proliferation-domains.

Background/aim: Sessile serrated polyps without dysplasia (SSPND) are characterized by crypts with serrated epithelium, albeit with irregular, corrupted shapes (CCS).

Patients And Methods: Cell proliferation was explored in the CCS from 60 SSPND and in the crypts from 12 normal colons. Sections were immuno-stained with the Ki-67 proliferation-cell (PC) marker, and with the p53 tumour-suppressor gene.

Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival.

Objective: Reflux promotes esophageal adenocarcinomas (EACs) creating a chronic inflammatory environment. Survival rates are low due to early local recurrences and distant metastasis. Hence, there is a need for new potential treatment options like immunotherapies.

Two intertwined compartments coexisting in sporadic conventional colon adenomas.

Sporadic conventional colon adenomas are microscopically built of 2 intertwined compartments: one on top, harboring the dysplastic tissue that defines their histo-biomolecular attributes, and the other below, composed of non-dysplastic crypts with corrupted shapes (CCS). The CCS of 306 colon adenomas revealed asymmetric, haphazardly-distributed proliferating cell-domains (PC). In contrast, the PC-domains in normal controls were symmetric, being limited to the lower thirds of the crypts.

ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia.

Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naïve cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT.

Correction: Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial.

Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)-positive disease.

Methods: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial.

Helminth Infections Suppress the Efficacy of Vaccination against Seasonal Influenza.

Helminth parasites infect more than a quarter of the human population and inflict significant changes to the immunological status of their hosts. Here, we analyze the impact of helminth infections on the efficacy of vaccinations using Litomosoides sigmodontis-infected mice. Concurrent helminth infection reduces the quantity and quality of antibody responses to vaccination against seasonal influenza.

The Normal Epithelium of Crypts Accruing Below Nonpolypoid Adenomas Thrives With Relocated Proliferating Cell-domains and p53-Up-regulated Cells.

Background/aim: Colonic crypts with normal epithelium albeit with corrupted shapes (CCS) were previously found beneath nonpolypoid adenomas (NPA). This study aimed to analyze the distribution of proliferating cells (PC) and p53-up-regulated cells in CCS.

Materials And Methods: Sections from 48 NPA were immunostained with the proliferating-marker Ki67 and against the tumor-suppressor protein p53.

How the Interplay Between the Commensal Microbiota, Gut Barrier Integrity, and Mucosal Immunity Regulates Brain Autoimmunity.

The intestinal barrier provides the host with a strong defense line against the external environment playing also a pivotal role in the crosstalk between the gut microbiota and the immune system. Notably, increasing lines of evidence concerning autoimmune disorders such as Multiple Sclerosis (MS) report an imbalance in both intestinal microbiota composition and mucosal immunity activation, along with an alteration of gut barrier permeability, suggesting this complex network plays a crucial role in modulating the course of autoimmune responses occurring in tissues outside the gut such as the central nervous system (CNS). Here, we review current knowledge on how gut inflammation and breakage of gut barrier integrity modulates the interplay between the commensal gut microbiota and the immune system and its role in shaping brain immunity.

Gonadal Failure Is Common in Long-Term Survivors of Childhood High-Risk Neuroblastoma Treated With High-Dose Chemotherapy and Autologous Stem Cell Rescue.

Neuroblastoma is the most common extra-cranial solid tumor in children. Intensive therapy including autologous stem-cell transplantation (HSCT) has improved the poor prognosis of high-risk neuroblastoma (HR-NBL) but may impair gonadal function. To investigate the gonadal function and fertility in long-term survivors of childhood HR-NBL.

Dissecting the Microscopic Anatomy of Colon Crypts in Non-dysplastic Sessile Serrated Polyps.

Background/aim: Sessile serrated polyps (SSP) are characterized by crypts with corrupted shapes (CCS).

Materials And Methods: The number of CCS and the lateral size of 60 non-dysplastic SSP (NDSSP) were investigated.

Results: Out of 60 NDSSP, 34 were small (≤9 mm) and 26, large (≥10 mm).

Outcome and presentation of heart failure in breast cancer patients: findings from a Swedish register-based study.

Aims: Heart failure (HF) patients diagnosed with breast cancer (BC) may have a higher risk of death, and different HF presentation and treatment than patients without BC.

Methods And Results: A total of 14 998 women with incident HF (iHF) or prevalent HF (pHF) enrolled in the Swedish HF Registry within and after 1 month since HF diagnosis, respectively, between 2008 and 2013. Patients were linked with the National Patient-, Cancer-, and Cause-of-Death Registry.

Telomere length regulators are activated in young men after pediatric kidney transplantation compared to healthy controls and survivors of childhood cancer-A cross-sectional study.

Chronic diseases are known to cause premature aging and frailty. Data about telomere length and telomere length-regulating proteins after pediatric KTx are scarce. Leukocyte telomere length and gene expression level of eight telomere-binding proteins were analyzed in 20 KTx recipients, eight childhood NBL survivors, and nine healthy controls.