Percutaneous Endoscopic Colostomy to Relieve Malignant Bowel Obstruction.

Background: Malignant bowel obstruction due to peritoneal carcinomatosis is a common problem. When surgery is not feasible in the context of a high intraperitoneal tumour burden, other techniques are required.

Case Report: We report the case of a 67-year-old female with malignant obstruction of the ascending colon.

Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis.

Importance: The prognosis of patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG) is poor. From current evidence, it remains unclear to what extent preoperative chemoradiotherapy (CRT) or preoperative and/or perioperative chemotherapy achieve better outcomes than surgery alone.

Objective: To assess the association of preoperative CRT and preoperative and/or perioperative chemotherapy in patients with AEG with overall survival and other outcomes.

Fully functional monocytic MDSC generation from the murine HoxB8 cell line.

Myeloid-derived suppressor cells (MDSC) play a crucial role in controlling T-cell responses, but their development and suppressor mechanisms are not fully understood. To study the molecular functions of MDSC, a large number of standardized cells are required. Traditionally, bone marrow (BM) has been used to generate myeloid cell types, including MDSC.

M-MDSC generation from mouse bone marrow with IL-3 reveals high expression and functional activity of arginase 1.

Myeloid-derived suppressor cells (MDSC) represent major regulators of immune responses, which can control T cells their inducible nitric oxide synthase (iNOS)- and arginase 1 (Arg1)-mediated effector functions. While GM-CSF is well documented to promote MDSC development, little is known about this potential of IL-3, an established growth factor for mast cells. Here, we show that IL-3, similar to GM-CSF, generates monocytic MDSC (M-MDSC) from murine bone marrow (BM) cells after 3 days of culture.

Early Detection of Pancreatic Cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy that is increasingly common. Screening for pancreatic cancer is not well established but might increase the chance of detection in early stages.

Summary: We conducted a literature search to summarize current recommendations and to give an overview of patient groups that may benefit from screening.

Expansion of regulatory T cells by CD28 superagonistic antibodies attenuates neurodegeneration in A53T-α-synuclein Parkinson's disease mice.

Background: Regulatory CD4CD25FoxP3 T cells (Treg) are a subgroup of T lymphocytes involved in maintaining immune balance. Disturbance of Treg number and impaired suppressive function of Treg correlate with Parkinson's disease severity. Superagonistic anti-CD28 monoclonal antibodies (CD28SA) activate Treg and cause their expansion to create an anti-inflammatory environment.

Guidelines for mouse and human DC generation.

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non-lymphoid tissues. This article provides protocols with top ticks and pitfalls for preparation and successful generation of mouse and human DC from different cellular sources, such as murine BM and HoxB8 cells, as well as human CD34 cells from cord blood, BM, and peripheral blood or peripheral blood monocytes. We describe murine cDC1, cDC2, and pDC generation with Flt3L and the generation of BM-derived DC with GM-CSF.

Fibroblastic reticular cells mitigate acute GvHD via MHCII-dependent maintenance of regulatory T cells.

Acute graft versus host disease (aGvHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) inflicted by alloreactive T cells primed in secondary lymphoid organs (SLOs) and subsequent damage to aGvHD target tissues. In recent years, Treg transfer and/or expansion has emerged as a promising therapy to modulate aGvHD. However, cellular niches essential for fostering Tregs to prevent aGvHD have not been explored.

Incidence and relative survival of pancreatic adenocarcinoma and pancreatic neuroendocrine neoplasms in Germany, 2009-2018. An in-depth analysis of two population-based cancer registries.

Background: Pancreatic neuroendocrine neoplasms are categorized as neuroendocrine tumors and neuroendocrine carcinomas. Until now, cancer registry reporting of pancreatic cancers does not include a stratification by these two subgroups. We studied the incidence and survival of pancreatic cancer with a special focus on pancreatic neuroendocrine neoplasms.

Highlights from the 2022 ASCO gastrointestinal cancer symposium: An overview by the EORTC gastrointestinal tract cancer group.

Recently, we have witnessed impressive diagnostic and therapeutic changes for gastrointestinal cancer patients. New challenges brought by the COVID-19 pandemic have led us to re-evaluate our work priorities. Thanks to the commendable resilience of both investigators and patients, however, clinical research never stopped.

Flt3L, LIF, and IL-10 combination promotes the selective in vitro development of ESAM cDC2B from murine bone marrow.

The development of two conventional dendritic cells (DC) subsets (cDC1 and cDC2) and the plasmacytoid DC (pDC) in vivo and in cultures of bone marrow (BM) cells is mediated by the growth factor Flt3L. However, little is known about the factors that direct the development of the individual DC subsets. Here, we describe the selective in vitro generation of murine ESAM CD103 XCR1 CD172a CD11b cDC2 from BM by treatment with a combination of Flt3L, LIF, and IL-10 (collectively named as FL10).

Interleukin-4 Responsive Dendritic Cells Are Dispensable to Host Resistance Against Infection.

IL-4 and IL-13 cytokines have been associated with a non-healing phenotype in murine leishmaniasis in -infected BALB/c mice as demonstrated in IL-4, IL-13 and IL-4Rα global knockout mouse studies. However, it is unclear from the studies which cell-type-specific IL-4/IL-13 signaling mediates protection to . Previous studies have ruled out a role for IL-4-mediated protection on CD4 T cells during infections.

Neurodegeneration by α-synuclein-specific T cells in AAV-A53T-α-synuclein Parkinson's disease mice.

Background: Antigen-specific neuroinflammation and neurodegeneration are characteristic for neuroimmunological diseases. In Parkinson's disease (PD) pathogenesis, α-synuclein is a known culprit. Evidence for α-synuclein-specific T cell responses was recently obtained in PD.

Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression.

Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4FoxP3 regulatory T cells (Tregs) are highly abundant amongst CD4 T cells providing an immune protective niche for different long-living cell populations, e.

Evaluation of autophagy mediators in myeloid-derived suppressor cells during human tuberculosis.

Myeloid-derived suppressor cells (MDSC) are induced during active TB disease to restore immune homeostasis but instead exacerbate disease outcome due to chronic inflammation. Autophagy, in conventional phagocytes, ensures successful clearance of M.tb.

Highlights from ASCO-GI 2021 from EORTC Gastrointestinal tract cancer group.

Last year the field of immunotherapy was finally introduced to GI oncology, with several changes in clinical practice such as advanced hepatocellular carcinoma or metastatic colorectal MSI-H. At the virtual ASCO-GI symposium 2021, several large trial results have been reported, some leading to a change of practice. Furthermore, during ASCO-GI 2021, results from early phase trials have been presented, some with potential important implications for future treatments.

Crizotinib: aseptic abscesses in multiple organs during treatment of EML4-ALK-positive NSCLC.

Purpose: We report a novel side effect of Crizotinib, an oral ALK inhibitor used in the treatment of non-small cell lung cancer (NSCLC) with activating rearrangement of EML4-ALK. It expands the known spectrum of complications of Crizotinib.

Methods: Clinical case report.

Conversion of Anergic T Cells Into Foxp3 IL-10 Regulatory T Cells by a Second Antigen Stimulus .

T cell anergy is a common mechanism of T cell tolerance. However, although anergic T cells are retained for longer time periods in their hosts, they remain functionally passive. Here, we describe the induction of anergic CD4 T cells by intravenous application of high doses of antigen and their subsequent conversion into suppressive Foxp3 IL-10 Tr1 cells but not Foxp3 Tregs.

Comments on the ambiguity of selected surface markers, signaling pathways and omics profiles hampering the identification of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSC) are important immune-regulatory cells but their identification remains difficult. Here, we provide a critical view on selected surface markers, transcriptional and translational pathways commonly used to identify MDSC by specific, their developmental origin and new possibilities by transcriptional or proteomic profiling. Discrimination of MDSC from their non-suppressive counterparts is a prerequisite for the development of successful therapies.

Revisiting Current Concepts on the Tolerogenicity of Steady-State Dendritic Cell Subsets and Their Maturation Stages.

The original concept stated that immature dendritic cells (DC) act tolerogenically whereas mature DC behave strictly immunogenically. Meanwhile, it is also accepted that phenotypically mature stages of all conventional DC subsets can promote tolerance as steady-state migratory DC by transporting self-antigens to lymph nodes to exert unique functions on regulatory T cells. We propose that in vivo 1) there is little evidence for a tolerogenic function of immature DC during steady state such as CD4 T cell anergy induction, 2) all tolerance as steady-state migratory DC undergo common as well as subset-specific molecular changes, and 3) these changes differ by quantitative and qualitative markers from immunogenic DC, which allows one to clearly distinguish tolerogenic from immunogenic migratory DC.

VLA-1 Binding to Collagen IV Controls Effector T Cell Suppression by Myeloid-Derived Suppressor Cells in the Splenic Red Pulp.

Myeloid-derived suppressor cells (MDSCs) represent a major population controlling T cell immune responses. However, little is known about their molecular requirements for homing and T cell interaction to mediate suppression. Here, we investigated the functional role of the homing and collagen IV receptor VLA-1 (α1β1-integrin) on GM-CSF generated murine MDSCs from wild-type (WT) and CD49a/α1-integrin () gene-deficient mice.

In Vitro Generation of Murine Myeloid-Derived Suppressor Cells, Analysis of Markers, Developmental Commitment, and Function.

Myeloid-derived suppressor cells (MDSC) appear at relatively low frequencies in diseased organs such as tumors or infection sites, but accumulate systemically in the spleen. So far MDSC have been reported in humans and experimental animals such as mice, rats, and nonhuman primates. Therefore, methods to generate MDSC in large amounts in vitro can serve as an additional tool to study their biology.