Gallstone may cause complications of cholecystitis, gallbladder gangrene, perforation, and related sepsis. This study aims to identify how CRP and immune cells change in patients with acute calculous cholecystitis based on the severity of disease.
Patients with acute calculous cholecystitis were categorized into three main groups-mild, moderate, and severe-based on the Tokyo guidelines. CRP, neutrophil, lymphocyte, helper T cells, cytotoxic T lymphocytes, and HLA-DR expression on CD14+ monocytes were measured using flow cytometry at the time of hospitalization from all patients and whether there were any differences between the groups was evaluated.
There were no significant differences in lymphocyte count, CD3+, CD4+, CD8+ cells, or CD4+/CD8+ ratios between groups. Though not significantly, lymphocyte count and CD3+ cells tended to decrease, while the CD4/CD8 ratio increased with disease severity. However, neutrophil count, Neutrophil/ Lymphocyte Ratio (NLR), CRP, and HLA-DR expression on CD14+ monocytes significantly increased with cholecystitis severity. The HLA-DR has 66.7% sensitivity and 92.9% specificity, while the CRP 78.6% sensitivity and 81.00% specificity and NLR 85.7% sensitivity and 76.2% specificity for predicting severe cholecystitis.
Evaluation of CRP, NLR, lymphocyte count, total CD3+ cells, CD4/CD8 ratio and HLA-DR expression on monocytes, at hospital admission, can provide clinicians with valuable information about the prognosis of the disease.

Type 3 innate lymphoid cells (ILC3) are important in tissue homeostasis. In the gut, ILC3 repair damaged epithelium and suppress inflammation. In allogeneic hematopoietic cell transplantation (HCT), ILC3 protect against graft-versus-host disease (GvHD), most likely by restoring tissue damage and preventing inflammation. We hypothesize that supplementing HCT grafts with interleukin-22 (IL-22)-producing ILC3 may prevent acute GvHD. We therefore explored ex vivo generation of human IL-22-producing ILC3 from hematopoietic stem and progenitor cells (HSPC) obtained from adult, neonatal and fetal sources. We established a stroma-free system culturing human cord blood-derived CD34+ HSPC with successive cytokine mixes for 5 weeks. We analyzed the presence of phenotypically defined ILC, their viability, proliferation and IL-22 production (after stimulation) by flow cytometry and enzyme-linked immunosorbent assay (ELISA). We found that the addition of recombinant human IL-15 and the enhancer of zeste homolog 1/2 inhibitor UNC1999 promoted ILC3 generation. Similar results were demonstrated when UNC1999 was added to CD34+ HSPC derived from healthy adult granulocyte colony-stimulating factor mobilized peripheral blood and bone marrow, but not fetal liver. UNC1999 did not negatively impact IL-22 production in any of the HSPC sources. Finally, we observed that autologous HSPC mobilized from the blood of adults with hematological malignancies also developed into ILC3, albeit with a significantly lower capacity. Together, we developed a stroma-free protocol to generate large quantities of IL-22-producing ILC3 from healthy adult human HSPC that can be applied for adoptive transfer to prevent GvHD after allogeneic HCT.
Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

HexaBody®-CD38 (GEN3014) is a hexamerization-enhanced human IgG1 that binds CD38 with high affinity. The E430G mutation in its Fc domain facilitates the natural process of antibody hexamer formation upon binding to the cell surface, resulting in increased binding of C1q and potentiated complement-dependent cytotoxicity (CDC).
Co-crystallization studies were performed to identify the binding interface of HexaBody-CD38 and CD38. HexaBody-CD38-induced CDC, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), trogocytosis, and apoptosis were assessed using flow cytometry assays using tumour cell lines, and MM patient samples (CDC). CD38 enzymatic activity was measured using fluorescence spectroscopy. Anti-tumour activity of HexaBody-CD38 was assessed in patient-derived xenograft mouse models in vivo.
HexaBody-CD38 binds a unique epitope on CD38 and induced potent CDC in multiple myeloma (MM), acute myeloid leukaemia (AML), and B-cell non-Hodgkin lymphoma (B-NHL) cells. Anti-tumour activity was confirmed in patient-derived xenograft models in vivo. Sensitivity to HexaBody-CD38 correlated with CD38 expression level and was inversely correlated with expression of complement regulatory proteins. Compared to daratumumab, HexaBody-CD38 showed enhanced CDC in cell lines with lower levels of CD38 expression, without increasing lysis of healthy leukocytes. More effective CDC was also confirmed in primary MM cells. Furthermore, HexaBody-CD38 efficiently induced ADCC, ADCP, trogocytosis, and apoptosis after Fc-crosslinking. Moreover, HexaBody-CD38 strongly inhibited CD38 cyclase activity, which is hypothesized to relieve immune suppression in the tumour microenvironment.
Based on these preclinical studies, a clinical trial was initiated to assess the clinical safety of HexaBody-CD38 in patients with MM.
Genmab.
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

In this exploratory prospective observational study on 40 small cell lung cancer (SCLC) patients treated with a combination of chemotherapy and immune checkpoint inhibitors, blood immune cells were characterized by multi-color flow cytometry at the baseline and at the third therapy cycle. The numbers of neutrophils and of T-, B-, and NK cells, as well as the frequency of HLA-DRlow monocytes, 6-SulfoLacNAc (slan)+ non-classical monocytes and circulating dendritic cell (DC) subtypes were determined. The prognostic value of the parameters was evaluated by the patient's survival analysis with overall survival (OS) as the primary endpoint. In addition, blood cell parameters from SCLC patients were compared to those from non-SCLC (NSCLC). The global median OS of patients was 10.4 ± 1.1 months. Disease progression (15% of patients) correlated with a higher baseline neutrophil/lymphocyte ratio (NLR), more HLA-DRlow monocytes, and lower NK cell and DC numbers. The risk factors for poor OS were the presence of brain/liver metastases, a baseline NLR ≥ 6.1, HLA-DRlow monocytes ≥ 21% of monocytes, slan+ non-classical monocytes < 0.12%, and/or CD1c+ myeloid DC < 0.05% of leukocytes. Lymphocytic subpopulations did not correlate with OS. When comparing biomarkers in SCLC versus NSCLC, SCLC had a higher frequency of brain/liver metastases, a higher NLR, the lowest DC frequencies, and lower NK cell numbers. Brain/liver metastases had a substantial impact on the survival of SCLC patients. At the baseline, 45% of SCLC patients, but only 24% of NSCLC patients, had between three and five risk factors. A high basal NLR, a high frequency of HLA-DRlow monocytes, and low levels of slan+ non-classical monocytes were associated with poor survival in all lung cancer histotypes. Thus, the blood immune cell signature might contribute to a better prediction of SCLC patient outcomes and may uncover the pathophysiological peculiarities of this tumor entity.

Lymphopenia, T cell subgroup changes, and cytokine level differences are important in the early diagnosis and treatment of Covid-19 cases and similar pandemics. We aimed to investigate the T cell, monocyte subgroups, and cytokine differences according to disease severity. A total of 46 volunteers were included in the study. According to disease status, there were three groups (control, mild, and severe). The age, gender, smoking status, temperature, heart rate and oxygen saturation, complete blood count, C-reactive protein (CRP) was noted, and flow cytometric analyses were performed for T cell and monocyte subgroups, and cytokine levels. Temperature, heart rate, SPO2 , white blood cell (WBC), lympocyte count, trombocyte count, neutrophil/lymphocyte ratio, D-dimer and CRP levels, lymphocyte %, lymphocyte/monocyte rate, monocyte subtypes (%), CD3+ , CD4+ , CD8+ cell counts, interleukin (IL)-1β, TNF-alpha, monocyte chemoattractant protein (MCP)-1, IL-6, IL-8, IL-10, IL-18, IL-23 were significantly different between groups. CRP, IL-8, neutrophil/lymphocyte ratio, NK cells (%) have positive correlation and negative correlation was observed at lymphocyte (count), lymphocyte (%), lymphocyte/monocyte, classical monocyte (%), lymphocyte (count), CD3+ (count), CD4+ (count). As conclusion, lymphocyte (%), Lymphocyte (count), CRP levels, CD3+ and CD4+ cell counts strongly correlate with disease severity are valuable parameters for determining the prognoses of Covid-19.
© 2022 Wiley Periodicals LLC.