Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.
Male ; Female ; Humans ; Middle Aged ; Aged ; Retrospective Studies ; Lymphoma, T-Cell, Peripheral/pathology* ; Killer Cells, Natural/pathology* ; Prognosis ; Immunophenotyping

Objective: To investigate the clinicopathological characteristics and prognosis of mature T/NK cell lymphomas with aberrant CD20 or CD79α expression. Methods: A retrospective analysis of 641 cases of mature T/NK cell lymphoma diagnosed from January 2014 to December 2020 was performed, and 14 cases of CD20-positive and one case of CD79α-positive mature T/NK-cell lymphoma were identified. Histological examination, immunohistochemical characterization, in situ hybridization for Epstein-Barr virus encoded early RNA (EBER), and PCR testing for immunoglobulin and T cell receptor (TCR) gene rearrangements were performed. Clinicopathological characteristics of these lymphomas were analyzed. Results: There were 13 males and 2 females, with a median age of 56 years. There were 8 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 3 cases of extranodal NK/T-cell lymphoma, nasal type (ENKTCL), 2 cases of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and 2 cases of angioimmunoblastic T-cell lymphoma (AITL). Twelve cases were stage Ⅲ or Ⅳ lymphomas. The prognosis was overall poor. The histology, immunophenotype and TCR gene rearrangement were not significantly different from the corresponding types of lymphoma. Ki-67 proliferation index was over 70% in all cases. The expression of CD20 or CD79α was weak and heterogeneous. All 15 case of Ig gene rearrangement were polyclonal. Conclusions: Mature T/NK cell lymphoma with abnormal expression of CD20 or CD79α is rare, commonly found in advanced stage, and associated with poor prognosis. The expression of CD20 or CD79α in these cases is weaker than the corresponding mature T/NK cell lymphomas, while its proliferation index is higher. Histomorphology, extensive immunoprofiling and molecular detection are required for accurate diagnosis.
Antigens, CD20 ; Epstein-Barr Virus Infections/complications* ; Female ; Herpesvirus 4, Human/genetics* ; Humans ; Killer Cells, Natural/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Male ; Middle Aged ; Receptors, Antigen, T-Cell ; Retrospective Studies

Objective To explore the clinical and laboratory characteristics and the prognosis of disseminated non-tuberculous mycobacteria(NTM)diseases in human immunodeficiency virus(HIV)negative patients. Methods Cases of disseminated NTM disease were retrospectively collected in Peking Union Medical College Hospital from January 2012 to October 2018.Clinical manifestations,laboratory findings,treatment,and prognosis of these cases were retrieved from the electronic medical record system. Results Among the 23 HIV negative patients with disseminated NTM disease,21 had underlying diseases,with rheumatoid immune disease(n=7)as the most common one.The main clinical manifestation was fever(n=23).Laboratory tests showed anemia [hemoglobin(85.78±25.47)g/L],hypoalbuminemia [albumin 29(27-32)g/L],elevated erythrocyte sedimentation rate [(85.73±43.78)mm/h] and hypersensitive C-reactive protein [(112.00±70.90)mg/L],and reduction of lymphocyte count [0.69(0.29-2.10)×10 /L].Lymphocyte subset analysis indicated reduction in CD4 T cells [213(113-775)/μl],CD8 T cells [267(99-457)/μl],B cells [39(4-165)/μl],and NK cells [88(32-279)/μl] and elevation of human leukocyte antigen-D related(HLA-DR),and CD38 expression in CD8 T cells [HLA-DR CD8 /CD8 ,60(40-68)%;CD38 CD8 /CD8 ,81(65-90)%].The most common species of NTM was Mycobacterium intracellular(n=6).Lymphocyte,CD8 T cell,B cell,and NK cell counts were significantly lower in dead patients than surviving patients(P =0.045,P=0.045,P=0.032,and P=0.010,respectively). Conclusions Disseminated NTM disease in HIV negative patients is mainly manifested as fever,anemia,hypoalbuminemia,and elevated inflammatory indicators.It is more likely to occur in immunocompromised patients.Patients with decreased lymphocytes,CD8 T cells,B cells and NK cells tend to have a poor prognosis.
Anemia ; B-Lymphocytes ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Fever ; HIV Seronegativity ; Humans ; Hypoalbuminemia ; Killer Cells, Natural ; Mycobacterium Infections, Nontuberculous ; diagnosis ; pathology ; Prognosis ; Retrospective Studies

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.
Animals ; Autoimmune Diseases ; immunology ; Humans ; Liver ; pathology ; Liver Diseases ; immunology ; Natural Killer T-Cells ; immunology

Immune thrombocytopenia (ITP) is recognized as a multifactorial cell-specific autoimmune disorder, and its pathogenesis is still not very clear. Traditional concept suggests that the platelet destruction mediated by autoantibodies is the pathophysiology mechanism of ITP, while many studies in recent years have shown that the abnormities of T lymphocyte, dendritic cell (DC), natural killer cell (NK), cytokine, programmed cell death (PCD), oxidative stress (OS), infection, pregnancy and drugs etc play an important role in the pathogenesis of ITP. Since the study of ITP has made a series of important achievements in recent years, this review focuses on the latest advance of studies on pathogenesis of ITP.
Apoptosis ; Autoantibodies ; blood ; Cytokines ; blood ; Dendritic Cells ; pathology ; Humans ; Killer Cells, Natural ; pathology ; Oxidative Stress ; Purpura, Thrombocytopenic, Idiopathic ; physiopathology ; T-Lymphocytes ; pathology

OBJECTIVEwe aimed to investigate the mutation and expression of BRAF gene in mature T/NK cell lymphoma tissues and cell lines, explore the correlation between gene alterations and clinicopathological features and clinical outcomes of mature T/NK cell lymphoma.

METHODSFirstly, we detected common mutant sites of BRAF (locus 1 799 mutation in exon 15 and loci 463, 465 and 468 mutation in exon 11) in lymphoma Jurkat, Hut-78 and YTS cell lines, normal peripheral blood lymphocytes, different types of mature T/NK cell lymphoma and reactive hyperplasia lymph nodes by direct sequencing. Then we measured the expression of BRAF in Jurkat, Hut-78, YTS cells and normal peripheral blood lymphocytes by real time-PCR and Western-blot detection. We also used immunohistochemistry (IHC) to detect the expression of BRAF in mature T/NK cell lymphoma tissues and reactive hyperplasia lymph nodes, and to analyze the correlation between the expression of BRAF and clinocopathological features and clinical outcomes.

RESULTSWe did not find common BRAF mutation in mature T/NK cell lymphoma tissues and cell lines, and the relatively expression of BRAF gene mRNA in normal peripheral blood lymphocytes, YTS, Hut-78 and Jurkat cells were 1.000, 5.207±0.013, 8.412±0.615 and 36.720±1.797, respectively, and protein expressions were 0.051±0.003, 0.102±0.013, 0.113±0.017 and 0.304±0.010, respectively, and the expression of BRAF in peripheral T cell lymphoma Jurkat cells was significantly higher than that of Hut-78, YTS cells and normal lymphocytes (P<0.05). Only 6 of 58 peripheral T cell lymphomas (10.3%) had positive BRAF expression, and were the subgroups of peripheral T cell lymphoma-unspecified type. The statistical data did not show any correlation between positive expression of BRAF and gender, age, clinical stage, location, lactate dehydrogenase in the 21 cases of peripheral T cell lymphoma-unspecified type (P<0.05), but the positive rate of BRAF in the effective treatment group (8.3%) was significantly lower than that of the invalid group (55.6%, P<0.05).

CONCLUSIONThe expression of BRAF gene may become a marker of malignant biological characteristics and clinical therapeutic target of peripheral T cell lymphoma.

Exons ; Humans ; Immunohistochemistry ; Killer Cells, Natural ; Lymphoma, T-Cell, Peripheral ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Pseudolymphoma ; genetics ; metabolism ; RNA, Messenger ; metabolism

OBJECTIVETo explore the effects of radiofrequency ablation(RFA) on immune system and lung metastasis in a mouse model of triple negative breast cancer 4T1.

METHODSMouse breast cancer 4T1 cells were injected into the right hind limb of female Bal B/c mice. When the tumor size was 6-8 mm in diameter, RFA was used to treat the transplanted breast cancer in mice. We examined the splenic lymphocyte subsets by flow cytometry at different time points after RFA. Fourteen days after treatment, we sacrificed the mice of both control and treatment groups, counted the number of lung metastatic nodules, and detected the changes of splenic lymphocyte subsets by flow cytometry.

RESULTSRFA basically eliminated the orthotopic carcinoma with a low local recurrence rate. After the RFA treatment, the amount of spleic CD4⁺ T cells, CD8⁺ T cells, B cells, NK and NKT cells was increased. Fourteen days after the RFA treatment, all mice were sacrificed, and the lung metastatic nodules were 24 ± 18 in the control group and 81 ± 35 in the RFA-treated group (P = 0.012). The mechanism of suppression of metastatic lung cancers was related to the increase of splenic CD4⁺ T cells, CD8⁺ T cells, B cells and NK cells, and the decrease of myeloid-derived suppressor cells.

CONCLUSIONSRFA can enhance the anti-tumor immunity and effectively inhibit lung metastasis of 4T1 cell-induced breast cancer, and has a good potential effect in the treatment of triple-negative breast cancer and the control of distant metastasis.

Animals ; B-Lymphocytes ; cytology ; CD4-Positive T-Lymphocytes ; cytology ; CD8-Positive T-Lymphocytes ; cytology ; Catheter Ablation ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural ; cytology ; Lung Neoplasms ; immunology ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Neoplasm Recurrence, Local ; Triple Negative Breast Neoplasms ; immunology ; pathology ; surgery ; Tumor Burden

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play crucial roles in a variety of diseases, including autoimmunity, infectious diseases, and cancers. However, little is known about the roles of these invariant T cells in acute cholecystitis. The purposes of this study were to examine the levels of MAIT cells and NKT cells in patients with acute cholecystitis and to investigate potential relationships between clinical parameters and these cell levels. Thirty patients with pathologically proven acute cholecystitis and 47 age- and sex-matched healthy controls were enrolled. Disease grades were classified according to the revised Tokyo guidelines (TG13) for the severity assessment for acute cholecystitis. Levels of MAIT and NKT cells in peripheral blood were measured by flow cytometry. Circulating MAIT and NKT cell numbers were significantly lower in acute cholecystitis patients than in healthy controls, and these deficiencies in MAIT cells and NKT cell numbers were associated with aging in acute cholecystitis patients. Notably, a reduction in NKT cell numbers was found to be associated with severe TG13 grade, death, and high blood urea nitrogen levels. The study shows numerical deficiencies of circulating MAIT and NKT cells and age-related decline of these invariant T cells. In addition, NKT cell deficiency was associated with acute cholecystitis severity and outcome. These findings provide an information regarding the monitoring of these changes in circulating MAIT and NKT cell numbers during the course of acute cholecystitis and predicting prognosis.
Aged ; Antibodies, Monoclonal/immunology ; Case-Control Studies ; Cholecystitis, Acute/*diagnosis/immunology/pathology ; Female ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear/cytology ; Male ; Middle Aged ; Natural Killer T-Cells/*cytology/immunology ; Patients ; Prognosis ; Severity of Illness Index ; T-Lymphocyte Subsets/*cytology/immunology

Epstein-Barr virus, a ubiquitous human herpesvirus, can induce both lytic and latent infections that result in a variety of human diseases, including lymphoproliferative disorders. The oncogenic potential of Epstein-Barr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, Epstein-Barr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. Epstein-Barr virus encodes a series of products that mimic several growth, transcription and anti-apoptotic factors, thus usurping control of pathways that regulate diverse homeostatic cellular functions and the microenvironment. However, the exact mechanism by which Epstein-Barr virus promotes oncogenesis and inflammatory lesion development remains unclear. Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases often have overlapping clinical symptoms as well as histologic and immunophenotypic features because both lymphoid cell types derive from a common precursor. Accurate classification of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases is a prerequisite for appropriate clinical management. Currently, the treatment of most T/natural killer cell lymphoproliferative diseases is less than satisfactory. Novel and targeted therapies are strongly required to satisfy clinical demands. This review describes our current knowledge of the genetics, oncogenesis, biology, diagnosis and treatment of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases.
Cell Transformation, Viral ; Epstein-Barr Virus Infections/*complications ; Herpesvirus 4, Human/*physiology ; Humans ; Killer Cells, Natural/immunology/metabolism/*pathology/*virology ; Lymphoproliferative Disorders/diagnosis/*etiology/therapy ; T-Lymphocytes/immunology/metabolism/*pathology/*virology

The development of highly immunodeficient mouse strains has allowed the reconstitution of functional human immune system components in mice. New-generation humanized mice generated in this manner have been extensively used for modeling viral infections that are exclusively human tropic. Epstein-Barr virus (EBV)-infected humanized mice reproduce cardinal features of EBV-associated B-cell lymphoproliferative disease and EBV-associated hemophagocytic lymphohistiocytosis (HLH). Erosive arthritis morphologically resembling rheumatoid arthritis (RA) has also been recapitulated in these mice. Low-dose EBV infection of humanized mice results in asymptomatic, persistent infection. Innate immune responses involving natural killer cells, EBV-specific adaptive T-cell responses restricted by human major histocompatibility and EBV-specific antibody responses are also elicited in humanized mice. EBV-associated T-/natural killer cell lymphoproliferative disease, by contrast, can be reproduced in a distinct mouse xenograft model. In this review, recent findings on the recapitulation of human EBV infection and pathogenesis in these mouse models, as well as their application to preclinical studies of experimental anti-EBV therapies, are described.
Animals ; Disease Models, Animal ; Epstein-Barr Virus Infections/complications/immunology/*virology ; Herpesvirus 4, Human/*physiology ; Heterografts ; Humans ; Killer Cells, Natural/pathology/virology ; Lymphoproliferative Disorders/etiology ; Mice ; Mice, SCID ; T-Lymphocytes/pathology/virology