INTRODUCTION

Parotid lymphoma is a rare occurrence, let alone a diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Salivary gland tumors commonly affect the parotid gland, although a primary malignant lesion rarely occurs, with an incidence of 0.5 to 3.0/100,000 population/year worldwide. This case report describes the presentation of this rare lymphoma. This also demonstrates the efficacy of standard of care chemotherapy with doxorubicin, vincristine, bleomycin, and dacarbazine with an anti-CD20 monoclonal antibody, rituximab (R-ABVD).

This is a case of a 44-year-old male with a gradually enlarging right preauricular mass. Biopsy and immunohistochemical staining confirmed a diagnosis of NLPHL Stage IIA. A total of six cycles of chemotherapy with R-ABVD was given. Follow-up PET CT showed resolution of FDG avid nodes localized near the surgically removed parotid gland, confirming complete remission.

Parotid malignancy only accounts for 5% of all head and neck tumors. NLPHL is even more rare, with an incidence of 1.5/1,000,000 population per year. The rarity of the case limits clinical trials for its treatment. Because of this, R-ABVD has been employed as a treatment of choice for intermediate-staged NLPHL. Overall response showed an 85% five-year progression-free survival and 99% overall survival.

This case report highlights the significance of early lymphoma detection despite its rarity among parotid tumors and prompt initiation of chemotherapy.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
Humans ; Receptors, Antigen, T-Cell, gamma-delta ; Immunotherapy, Adoptive ; T-Lymphocytes ; Immunotherapy ; Neoplasms/therapy*

Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.
Animals ; Mice ; Colitis/chemically induced* ; Immunity, Innate ; Intestine, Small ; Lymphocytes ; Mice, Inbred C57BL

Objective To explore the phenotypic conversion of regulatory T cells (Tregs) in the lungs of mice with bronchopulmonary dysplasia (BPD)-affected mice. Methods A total of 20 newborn C57BL/6 mice were divided into air group and hyperoxia group, with 10 mice in each group. The BPD model was established by exposing the newborn mice to hyperoxia. Lung tissues from five mice in each group were collected on postnatal days 7 and 14, respectively. Histopathological changes of the lung tissues was detected by HE staining. The expression level of surfactant protein C (SP-C) in the lung tissues was examined by Western blot analysis. Flow cytometry was performed to assess the proportion of FOXP3⁺ Tregs and RORγt⁺FOXP3⁺ Tregs in CD4⁺ lymphocytes. The concentrations of interleukin-17A (IL-17A) and IL-6 in lung homogenate were measured by using ELISA. Spearman correlation analysis was used to analyze the correlation between FOXP3⁺Treg and the expression of SP-C and the correlation between RORγt⁺FOXP3⁺ Tregs and the content of IL-17A and IL-6. Results The hyperoxia group exhibited significantly decreased levels of SP-C and radical alveolar counts in comparison to the control group. The proportion of FOXP3⁺Tregs was reduced and that of RORγt⁺FOXP3⁺Tregs was increased. IL-17A and IL-6 concentrations were significantly increased. SP-C was positively correlated with the expression level of RORγt⁺FOXP3⁺ Tregs. RORγt⁺FOXP3⁺ Tregs and IL-17A and IL-6 concentrations were also positively correlated. Conclusion The number of FOXP3⁺ Tregs in lung tissue of BPD mice is decreased and converted to RORγt⁺ FOXP3⁺ Tregs, which may be involved in hyperoxy-induced lung injury.
Animals ; Mice ; Mice, Inbred C57BL ; Bronchopulmonary Dysplasia ; T-Lymphocytes, Regulatory ; Interleukin-17 ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Hyperoxia ; Interleukin-6 ; Forkhead Transcription Factors ; Lung

In the tumor microenvironment, metabolic reprogramming can impact metabolic characteristics of T cells, thus inducing immunosuppression to promote tumor immune escape. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in regulating diverse functions of various immune cells. This review mainly focuses on the molecular mechanism of mTOR signaling in regulating cellular energy metabolism process, and the activation status of mTOR signaling under different nutritional environments. In addition, it also summarizes the role of the mTOR signaling in regulatory T cell (Tregs) metabolism and function in current studies, and evaluates the potential of mTOR as a clinical immunotherapeutic target and its current application challenges.
Immunosuppression Therapy ; Metabolic Reprogramming ; Signal Transduction ; Sirolimus ; T-Lymphocytes, Regulatory ; TOR Serine-Threonine Kinases ; Humans

Hepatocellular carcinoma (HCC) is well characterized as a heterogeneous disease. Its late-stage diagnosis and chemotherapy resistance make it one of the refractory tumors in China. Natural killer (NK) cells play a significant role in immune surveillance. However, NK cells become dysfunctional in the progression of HCC, leading to tumor immune escape. This article reviews the recent progress on different strategies of NK cell-based immunotherapy in treating HCC, including direct adoptive NK cell transfer, gene engineering in NK cell, NK cell receptor targeting, immunosuppressive microenvironment modification, and tumor toxicity enhancement by cytokines or traditional Chinese medicine. These NK cell-based strategies have shown promising therapeutic potential.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy ; Killer Cells, Natural ; Receptors, Natural Killer Cell ; Tumor Microenvironment

Objective To investigate the effect of human platelet-rich plasma-derived exosomes(PRP-exos)on the proliferation of Schwann cell(SC)cultured in vitro. Methods PRP-exos were extracted by polymerization-precipitation combined with ultracentrifugation.The morphology of PRP-exos was observed by transmission electron microscopy,and the concentration and particle size distribution of PRP-exos were determined by nanoparticle tracking analysis.Western blotting was employed to determine the expression of the marker proteins CD63,CD81,and CD9 on exosome surface and the platelet membrane glycoprotein CD41.The SCs of rats were isolated and cultured,and the expression of the SC marker S100β was detected by immunofluorescence staining.The fluorescently labeled PRP-exos were co-cultured with SCs in vitro for observation of their interaction.EdU assay was employed to detect the effect of PRP-exos on SC proliferation,and CCK-8 assay to detect the effects of PRP-exos at different concentrations(0,10,20,40,80,and 160 μg/ml)on SC proliferation. Results The extracted PRP-exos appeared as uniform saucer-shaped vesicles with the average particle size of(122.8±38.7)nm and the concentration of 3.5×10¹² particles/ml.CD63,CD81,CD9,and CD41 were highly expressed on PRP-exos surface(P<0.001,P=0.025,P=0.004,and P=0.032).The isolated SCs expressed S100β,and PRP-exos could be taken up by SCs.PRP-exos of 40,80,and 160 μg/ml promoted the proliferation of SCs,and that of 40 μg/ml showed the best performance(all P<0.01). Conclusions High concentrations of PRP-exos can be extracted from PRP.PRP-exos can be taken up by SCs and promote the proliferation of SCs cultured in vitro.
Humans ; Rats ; Animals ; Exosomes/metabolism* ; Platelet-Rich Plasma ; Schwann Cells ; Coculture Techniques ; Cell Proliferation ; Cells, Cultured

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.
Animals ; Receptors, Chimeric Antigen/metabolism* ; Multiple Myeloma/metabolism* ; Killer Cells, Natural/metabolism* ; Immunotherapy, Adoptive/methods* ; Tumor Microenvironment

Objective:b> To determine the ability of the ratio of platelet to lymphocyte (PLR) for predicting extubation failure in septic patients receiving invasive mechanical ventilation (IMV). Methods:b> The retrospective cohort study was conducted in ICU at Beijing Chao-Yang Hospital Shijingshan District, Capital Medical University in China from January, 2010 to December, 2019, including patients with sepsis who received IMV. 180 patients were enrolled in the study, including 111 male and 69 female, with the age range of 23-93 years and the median age of 76 years, and with an average age of 71.22 years. The medical records were reviewed, such as age, sex, acute physiology and chronic health evaluation II (APACHEII), sequential organ failure assessment (SOFA), spontaneous breathing trial (SBT) outcome, weaning outcome, complete blood count before SBT. According to weaning outcome, patients were divided into weaning failure and weaning success group. The difference of PLR, white blood cell(WBC), C-reaction protein (CRP) and procalcitonin (PCT) were compared between weaning failure and success group. Receiver-operating characteristics (ROC) curves and multivariate logistical regression analysis were employed to analyze the performance of these inflammatory markers for predicting weaning failure in patients with sepsis. Results:b> 180 patients with sepsis were included in the study and 37 patients (20.5%) experienced weaning failure (31 SBT failure and 6 extubation failure after successful SBT). PLR was higher in weaning failure group than that in weaning success group (Z=-5.793,P<0.001). Other inflammation biomarkers such as WBC, CRP and PCT were also higher in weaning failure group than that in weaning success group(Z=-4.356, -3.118 and -2.743, P<0.001, 0.002 and 0.006, respectively). According to ROC curves, PLR has a better predictive ability for weaning failure (AUC=0.809,95%CI 0.733-0.885) when compared to WBC (AUC=0.773,95%CI 0.648-0.817), CRP (AUC=0.666,95%CI 0.577-0.755) and PCT (AUC=0.603,95%CI 0.508-0.698). The cutoff value of PLR for predicting weaning failure was 257.69 with sensitivity 78.38%, specificity 76.22%, and diagnostic accuracy 71.66%. According to multivariate logistic regression analyses, PLR>257.69 was an independent risk factor for predicting weaning failure in patients with sepsis. Conclusions:b> PLR may be a valuable biomarker for predicting weaning failure in septic patients receiving IMV, and the patients with higher PLR should be handled with caution since they are at higher risk of weaning failure, and some more effective treatment should be in consideration after extubation.
Humans ; Male ; Female ; Aged ; Young Adult ; Adult ; Middle Aged ; Aged, 80 and over ; Respiration, Artificial ; Retrospective Studies ; Sepsis/diagnosis* ; Procalcitonin ; C-Reactive Protein ; Biomarkers ; ROC Curve ; Lymphocytes