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Cellular & Molecular Biology Letters May 2024The role of the scavenger receptor CD36 in cell metabolism and the immune response has been investigated mainly in macrophages, dendritic cells, and T cells. However,...
BACKGROUND
The role of the scavenger receptor CD36 in cell metabolism and the immune response has been investigated mainly in macrophages, dendritic cells, and T cells. However, its involvement in B cells has not been comprehensively examined.
METHODS
To investigate the function of CD36 in B cells, we exposed Cd36MB1 mice, which lack CD36 specifically in B cells, to apoptotic cells to trigger an autoimmune response. To validate the proteins that interact with CD36 in primary B cells, we conducted mass spectrometry analysis following anti-CD36 immunoprecipitation. Immunofluorescence and co-immunoprecipitation were used to confirm the protein interactions.
RESULTS
The data revealed that mice lacking CD36 in B cells exhibited a reduction in germinal center B cells and anti-DNA antibodies in vivo. Mass spectrometry analysis identified 30 potential candidates that potentially interact with CD36. Furthermore, the interaction between CD36 and the inhibitory Fc receptor FcγRIIb was first discovered by mass spectrometry and confirmed through immunofluorescence and co-immunoprecipitation techniques. Finally, deletion of FcγRIIb in mice led to decreased expression of CD36 in marginal zone B cells, germinal center B cells, and plasma cells.
CONCLUSIONS
Our data indicate that CD36 in B cells is a critical regulator of autoimmunity. The interaction of CD36-FcγRIIb has the potential to serve as a therapeutic target for the treatment of autoimmune disorders.
Topics: Animals; CD36 Antigens; Receptors, IgG; B-Lymphocytes; Autoimmune Diseases; Mice; Germinal Center; Mice, Inbred C57BL; Protein Binding; Mice, Knockout; Autoimmunity
PubMed: 38762740
DOI: 10.1186/s11658-024-00593-7 -
Nature Communications May 2024The naked mole-rat (Heterocephalus glaber) is a long-lived rodent species showing resistance to the development of cancer. Although naked mole-rats have been reported to...
The naked mole-rat (Heterocephalus glaber) is a long-lived rodent species showing resistance to the development of cancer. Although naked mole-rats have been reported to lack natural killer (NK) cells, γδ T cell-based immunity has been suggested in this species, which could represent an important arm of the immune system for antitumor responses. Here, we investigate the biology of these unconventional T cells in peripheral tissues (blood, spleen) and thymus of the naked mole-rat at different ages by TCR repertoire profiling and single-cell gene expression analysis. Using our own TCR annotation in the naked mole-rat genome, we report that the γδ TCR repertoire is dominated by a public invariant Vγ4-2/Vδ1-4 TCR, containing the complementary-determining-region-3 (CDR3)γ CTYWDSNYAKKLF / CDR3δ CALWELRTGGITAQLVF that are likely generated by short-homology-repeat-driven DNA rearrangements. This invariant TCR is specifically found in γδ T cells expressing genes associated with NK cytotoxicity and is generated in both the thoracic and cervical thymus of the naked mole-rat until adult life. Our results indicate that invariant Vγ4-2/Vδ1-4 NK-like effector T cells in the naked mole-rat can contribute to tumor immunosurveillance by γδ TCR-mediated recognition of a common molecular signal.
Topics: Animals; Mole Rats; Receptors, Antigen, T-Cell, gamma-delta; Thymus Gland; Killer Cells, Natural; Spleen; Complementarity Determining Regions; Natural Killer T-Cells
PubMed: 38762584
DOI: 10.1038/s41467-024-48652-z -
BMC Pulmonary Medicine May 2024The application of radiomics in thoracic lymph node metastasis (LNM) of lung adenocarcinoma is increasing, but diagnostic performance of radiomics from primary tumor to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The application of radiomics in thoracic lymph node metastasis (LNM) of lung adenocarcinoma is increasing, but diagnostic performance of radiomics from primary tumor to predict LNM has not been systematically reviewed. Therefore, this study sought to provide a general overview regarding the methodological quality and diagnostic performance of using radiomic approaches to predict the likelihood of LNM in lung adenocarcinoma.
METHODS
Studies were gathered from literature databases such as PubMed, Embase, the Web of Science Core Collection, and the Cochrane library. The Radiomic Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were both used to assess the quality of each study. The pooled sensitivity, specificity, and area under the curve (AUC) of the best radiomics models in the training and validation cohorts were calculated. Subgroup and meta-regression analyses were also conducted.
RESULTS
Seventeen studies with 159 to 1202 patients each were enrolled between the years of 2018 to 2022, of which ten studies had sufficient data for the quantitative evaluation. The percentage of RQS was between 11.1% and 44.4% and most of the studies were considered to have a low risk of bias and few applicability concerns in QUADAS-2. Pyradiomics and logistic regression analysis were the most commonly used software and methods for radiomics feature extraction and selection, respectively. In addition, the best prediction models in seventeen studies were mainly based on radiomics features combined with non-radiomics features (semantic features and/or clinical features). The pooled sensitivity, specificity, and AUC of the training cohorts were 0.84 (95% confidence interval (CI) [0.73-0.91]), 0.88 (95% CI [0.81-0.93]), and 0.93(95% CI [0.90-0.95]), respectively. For the validation cohorts, the pooled sensitivity, specificity, and AUC were 0.89 (95% CI [0.82-0.94]), 0.86 (95% CI [0.74-0.93]) and 0.94 (95% CI [0.91-0.96]), respectively.
CONCLUSIONS
Radiomic features based on the primary tumor have the potential to predict preoperative LNM of lung adenocarcinoma. However, radiomics workflow needs to be standardized to better promote the applicability of radiomics.
TRIAL REGISTRATION
CRD42022375712.
Topics: Humans; Lung Neoplasms; Adenocarcinoma of Lung; Lymphatic Metastasis; Predictive Value of Tests; Lymph Nodes; Tomography, X-Ray Computed; Sensitivity and Specificity; Radiomics
PubMed: 38762472
DOI: 10.1186/s12890-024-03020-x -
Journal of Vascular Surgery. Venous and... May 2024Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, Supraclavicular...
Synchronous Supraclavicular Vascularized Lymph Node Transfer and Liposuction for Gynecological Cancer-Related Lower Extremity Lymphedema: A Clinical Comparative Analysis of Three Different Procedures.
OBJECTIVE
Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, Supraclavicular vascularized lymph node transfer (SC-VLNT) is a favoured approach in the treatment of lymphedema, and there is a trend toward combination technology. This study conducts a comparative analysis of three techniques for treating GC-LEL with simultaneous SC-VLNT and liposuction.
METHODS
A cohort of 35 patients with GC-LEL was examined, comprising thirteen patients underwent single lymph nodes flap with a skin paddle (SLNF+P), twelve received single lymph nodes flap without a skin paddle (SLNF), and ten accepted dual lymph nodes flap without a skin paddle (DLNF). Patient demographics and outcomes were meticulously documented, covering intra- and post-operative variables.
RESULTS
The median limb volume reduction were 56.4% (SLNF+P), 60.8% (SLNF), and 50.5% (DLNF) in stage II, and 54.0% (SLNF+P), 59.8% (SLNF), and 54.4% (DLNF) in stage III. DLNF group procedures entailed longer flap harvesting and transplantation times. The SLNF+P group, on average, had an 8-day postoperative hospitalization, longer than others. All patient noted subjective improvements in Lymphedema Quality of Life (LYMQOL) scores, with lymphoscintigraphy revealing enhanced lymphatic flow in 29 of the 35 cases. A notable decrease in cellulitis incidence was observed. Additionally, the occurrence of cellulitis decreased significantly, except for DLNF (Stage Ⅱ). The median follow-up time was 16 months (range, 12 to 36 months), with no reported severe postoperative complications.
CONCLUSION
For advanced GC-LEL, SLNF combined with liposuction is a preferred treatment, offering fewer complications, shorter operative time, and hospitalization.
PubMed: 38761979
DOI: 10.1016/j.jvsv.2024.101905 -
Frontiers in Immunology 2024Cryptosporidiosis is a poorly controlled zoonosis caused by an intestinal parasite, , with a high prevalence in livestock (cattle, sheep, and goats). Young animals are...
INTRODUCTION
Cryptosporidiosis is a poorly controlled zoonosis caused by an intestinal parasite, , with a high prevalence in livestock (cattle, sheep, and goats). Young animals are particularly susceptible to this infection due to the immaturity of their intestinal immune system. In a neonatal mouse model, we previously demonstrated the importance of the innate immunity and particularly of type 1 conventional dendritic cells (cDC1) among mononuclear phagocytes (MPs) in controlling the acute phase of infection. These immune populations are well described in mice and humans, but their fine characterization in the intestine of young ruminants remained to be further explored.
METHODS
Immune cells of the small intestinal Peyer's patches and of the distal jejunum were isolated from naive lambs and calves at different ages. This was followed by their fine characterization by flow cytometry and transcriptomic analyses (q-RT-PCR and single cell RNAseq (lamb cells)). Newborn animals were infected with , clinical signs and parasite burden were quantified, and isolated MP cells were characterized by flow cytometry in comparison with age matched control animals.
RESULTS
Here, we identified one population of macrophages and three subsets of cDC (cDC1, cDC2, and a minor cDC subset with migratory properties) in the intestine of lamb and calf by phenotypic and targeted gene expression analyses. Unsupervised single-cell transcriptomic analysis confirmed the identification of these four intestinal MP subpopulations in lamb, while highlighting a deeper diversity of cell subsets among monocytic and dendritic cells. We demonstrated a weak proportion of cDC1 in the intestine of highly susceptible newborn lambs together with an increase of these cells within the first days of life and in response to the infection.
DISCUSSION
Considering cDC1 importance for efficient parasite control in the mouse model, one may speculate that the cDC1/cDC2 ratio plays also a key role for the efficient control of in young ruminants. In this study, we established the first fine characterization of intestinal MP subsets in young lambs and calves providing new insights for comparative immunology of the intestinal MP system across species and for future investigations on host-Cryptosporidium interactions in target species.
Topics: Animals; Cryptosporidiosis; Cryptosporidium parvum; Sheep; Cattle; Homeostasis; Dendritic Cells; Phagocytes; Animals, Newborn; Sheep Diseases; Peyer's Patches; Macrophages; Intestines; Ruminants
PubMed: 38756777
DOI: 10.3389/fimmu.2024.1379798 -
Frontiers in Immunology 2024Frequencies and phenotypes of immune cells differ between neonates and adults in association with age-specific immune responses. Lymph nodes (LN) are critical tissue...
Frequencies and phenotypes of immune cells differ between neonates and adults in association with age-specific immune responses. Lymph nodes (LN) are critical tissue sites to quantify and define these differences. Advances in flow cytometry have enabled more multifaceted measurements of complex immune responses. Tissue processing can affect the immune cells under investigation that influence key findings. To understand the impact on immune cells in the LN after processing for single-cell suspension, we compared three dissociation protocols: enzymatic digestion, mechanical dissociation with DNase I treatment, and mechanical dissociation with density gradient separation. We analyzed cell yields, viability, phenotypic and maturation markers of immune cells from the lung-draining LN of neonatal and adult mice two days after intranasal respiratory syncytial virus (RSV) infection. While viability was consistent across age groups, the protocols influenced the yield of subsets defined by important phenotypic and activation markers. Moreover, enzymatic digestion did not show higher overall yields of conventional dendritic cells and macrophages from the LN. Together, our findings show that the three dissociation protocols have similar impacts on the number and viability of cells isolated from the neonatal and adult LN. However, enzymatic digestion impacts the mean fluorescence intensity of key lineage and activation markers that may influence experimental findings.
Topics: Animals; Lymph Nodes; Mice; Animals, Newborn; Respiratory Syncytial Virus Infections; Phenotype; Lymphocytes; Myeloid Cells; Cell Separation; Flow Cytometry; Immunophenotyping; Female; Mice, Inbred C57BL; Dendritic Cells
PubMed: 38756770
DOI: 10.3389/fimmu.2024.1368118 -
BMC Medicine May 2024Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics,...
BACKGROUND
Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear.
METHODS
Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics.
RESULTS
From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells.
CONCLUSIONS
Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.
Topics: Osteosarcoma; Tumor Microenvironment; Humans; Single-Cell Analysis; Bone Neoplasms; Lymph Nodes; Lymphatic Metastasis; Transcriptome; Animals; Mice; Cell Line, Tumor; Gene Expression Profiling
PubMed: 38755647
DOI: 10.1186/s12916-024-03319-w -
BMC Cancer May 2024Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the...
Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.
BACKGROUND
Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery.
METHODS
In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern.
RESULTS
From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences.
CONCLUSIONS
We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.
Topics: Humans; Male; Female; Middle Aged; Esophageal Neoplasms; Retrospective Studies; Lymphatic Metastasis; Neoplasm Recurrence, Local; Aged; Lymph Nodes; Lymph Node Excision; Esophageal Squamous Cell Carcinoma; Esophagectomy; Adult; Prognosis; China; Neoplasm Staging
PubMed: 38755542
DOI: 10.1186/s12885-024-12297-4 -
Communications Biology May 2024B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood...
B cells are important in tuberculosis (TB) immunity, but their role in the human lung is understudied. Here, we characterize B cells from lung tissue and matched blood of patients with TB and found they are decreased in the blood and increased in the lungs, consistent with recruitment to infected tissue, where they are located in granuloma associated lymphoid tissue. Flow cytometry and transcriptomics identify multiple B cell populations in the lung, including those associated with tissue resident memory, germinal centers, antibody secretion, proinflammatory atypical B cells, and regulatory B cells, some of which are expanded in TB disease. Additionally, TB lungs contain high levels of Mtb-reactive antibodies, specifically IgM, which promotes Mtb phagocytosis. Overall, these data reveal the presence of functionally diverse B cell subsets in the lungs of patients with TB and suggest several potential localized roles that may represent a target for interventions to promote immunity or mitigate immunopathology.
Topics: Humans; B-Lymphocytes; Lung; Mycobacterium tuberculosis; Phenotype; Tuberculosis; Tuberculosis, Pulmonary; B-Lymphocyte Subsets; Male; Female; Adult
PubMed: 38755239
DOI: 10.1038/s42003-024-06282-7 -
Scientific Reports May 2024The preoperative distinguishment of lymph nodes (LN) with metastasis plays a pivotal role in guiding the surgical extension for gastric cancer (GC). We aim to identify...
The preoperative distinguishment of lymph nodes (LN) with metastasis plays a pivotal role in guiding the surgical extension for gastric cancer (GC). We aim to identify the preparative risk factors for LN metastasis in GC patients. We retrospectively reviewed 424 patients who underwent radical GC resection in our medical center between Jan 2011 and Dec 2018. Multivariate logistic regression was employed to identify risk factors for LN metastasis, while multivariate COX regression was utilized to evaluate prognostic factors. The median overall survival of patients with or without LN metastases was 31 and 58 months, respectively. In multivariate analysis, lower albumin (OR = 0.512; P = 0.004) and prealbumin (OR = 0.367, P = 0.001) and higher CEA (OR = 3.178, P < 0.001), CA199 (OR = 2.278, P = 0.002) and platelets (OR = 1.697, P = 0.017) were found to be significantly associated with LN metastasis. In survival analysis, older age (HR = 1.712), larger tumors (HR = 1.082), higher D-dimer (HR = 1.561) and CA199 (HR = 1.553), advanced staging (stage II, HR = 3.446; stage III-IV, HR = 11.089), lower prealbumin levels (lower level for reference, HR = 0.63), and absence of adjuvant chemotherapy (HR = 0.396) was discovered to be associated with poorer overall survival (all P < 0.05). In conclusion, our results demonstrated that preoperative prealbumin-bound tumor markers can effectively predict LN metastasis. Additionally, prealbumin was found to possess prognostic value as well.
Topics: Humans; Stomach Neoplasms; Male; Female; Lymphatic Metastasis; Middle Aged; Prognosis; Aged; Retrospective Studies; Lymph Nodes; Risk Factors; Neoplasm Staging; Adult; Biomarkers, Tumor; Preoperative Period; Aged, 80 and over
PubMed: 38755185
DOI: 10.1038/s41598-024-61671-6