Human CD4- CD8- Invariant Natural Killer T Cells Promote IgG Secretion from B Cells Stimulated by Cross-Linking of Their Antigen Receptors

Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4+ CD8β- (CD4) and CD4- CD8β- [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19+CD27- (naïve) and CD19+CD27+ (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.

iNKT细胞与缺血性脑卒中后免疫抑制关系的研究进展

缺血性脑卒中即各种脑血管病变导致的脑组织供血供氧障碍从而出现的神经系统损伤。卒中后免疫抑制诱发的严重感染是影响患者生存预后的重要因素。抗生素治疗受到药物耐药性增加的限制,因此,免疫调节治疗受到广泛的关注。卒中后,不变的自然杀伤T细胞(iNKT)在免疫抑制中发挥重要作用,其作为上游调节免疫系统中的CD4^(+)T和CD8^(+)T细胞,促使免疫系统Th1向Th2改变,从而导致卒中后免疫抑制。用α-半乳糖神经酰胺(α-GalCer)直接调节iNKT细胞或通过阻断去甲肾上腺素能神经递质有助于减少卒中后的感染率。但iNKT细胞如何被远距离激活,如何在卒中后推动免疫系统改变的机制尚不明确。该文就iNKT细胞的生物学特征、功能及如何影响卒中后免疫抑制做一综述。

Subgroups of peripheral immune effector cells in cervical cancer patients are more sensitive to radiation therapy than chemotherapy

Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.

Intrahepatic natural killer T cell populations are increased in human hepatic steatosis

AIM: To determine if natural killer T cell (NKT) populations are affected in nonalcoholic fatty liver disease (NAFLD). METHODS: Patients undergoing bariatric surgery underwent liver biopsy and blood sampling during surgery. The biopsy was assessed for steatosis and immunocyte infiltration. Intrahepatic lymphocytes (IHLs) were isolated from the remainder of the liver biopsy, and peripheral blood mononuclear cells (PBMCs) were isolated from the blood. Expression of surface proteins on both IHLs and PBMCs were quantified using flow cytometry. RESULTS: Twenty-seven subjects participated in thisstudy. Subjects with moderate or severe steatosis had a higher percentage of intrahepatic CD3+/CD56+ NKT cells (38.6%) than did patients with mild steatosis (24.1%, P = 0.05) or those without steatosis (21.5%, P = 0.03). Patients with moderate to severe steatosis also had a higher percentage of NKT cells in the blood (12.3%) as compared to patients with mild steatosis (2.5% P = 0.02) and those without steatosis (5.1%, P = 0.05). CONCLUSION: NKT cells are significantly increased in the liver and blood of patients with moderate to severe steatosis and support the role of NKT cells in NAFLD.

Association of the frequency of peripheral natural killer T cells with nonalcoholic fatty liver disease

AIM: To investigate whether changes in the frequencyof peripheral natural killer T (NKT) cells were correlatedwith liver disease in patients who had metabolicpredispositions to nonalcoholic fatty liver disease(NAFLD).METHODS: Peripheral blood samples were obtainedfrom 60 Chinese NAFLD patients and 60 age and gendermatched healthy controls. The frequency of peripheralNKT cells was detected by flow cytometry. Clinical andlaboratory data were collected for further analysis. RESULTS: NAFLD patients had a lower frequencyof peripheral NKT cells than healthy controls (1.21%± 0.06% vs 1.62% ± 0.07%, P < 0.001). Furtheranalysis revealed that the frequency of peripheralNKT cells was negatively correlated with body massindex, waist circumference and serum levels of alanineaminotransferase. Logistic regression analysis revealedthat elevated body mass index [hazard ratio (HR):2.991], aspartate aminotransferase levels (HR: 1.148)and fasting blood sugar (HR: 3.133) increased the riskof NAFLD, whereas an elevated frequency of peripheralNKT cells (HR: 0.107) decreased the risk. CONCLUSION: Changes in the frequency of peripheralNKT cells were correlated with NAFLD and a decreasedfrequency of peripheral NKT cells was a risk factor forNAFLD.

CD30 expression in extranodal natural killer/T-cell lymphoma,nasal type among 622 cases of mature T-cell and natural killer-cell lymphoma at a single institution in South China

Background:Mature T-cell and natural killer(NK)-cell lymphomas compose a heterogeneous group of non-Hodgkin lymphomas,and extranodal NK/T-cell lymphoma,nasal type(ENKTL) is an aggressive subtype with sporadic CD30 expression.However,the significance of CD30 expression in ENKTL is controversial.We aimed to classify a large cohort of patients with mature T-cell and NK-cell lymphomas according to the 2016 World Health Organization(WHO) classification guidelines and to study the association between CD30 expression and prognosis of patients with ENKTL.Methods:We selected consecutive patients with mature T-cell and NK-cell lymphomas who attended our institution between September 1,2009 and August 31,2013.We classified the lymphomas according to the 2016 revision of the WHO classification of lymphoid neoplasms,analyzed the associations between CD30 expression and clinicopathologic features of ENKTL patients,and evaluated the prognostic implications of CD30 expression.Results:We identified 622 consecutive patients with mature T-cell and NK-cell lymphomas,including 317(51.0%)patients with ENKTL.In addition,CD30 expression was detected in 43(47.3%) of a subset of 91 patients with ENKTL.No clinicopathologic features were associated with CD30 expression,and CD30 positivity showed no prognostic significance in patients with ENKTL.Conclusions:ENKTL is the most common type of mature T-cell and NK-cell lymphoma diagnosed at our institution.CD30 is frequently expressed in ENKTL and represents a therapeutic target;however,it may not be a prognostic marker.

Updating targets for natural killer/T-cell lymphoma immunotherapy

Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The current treatment methods for NKTCL are associated with several drawbacks.For example,chemotherapy can lead to drug resistance,while treatment with radiotherapy alone is inadequate and results in frequent relapses.Moreover,hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts.In recent years,immunotherapy has shown good clinical results and has become a hot spot in cancer research.Clinical activity of targeted antibodies,such as daratumumab(anti-CD38 antibody)and brentuximab vedotin(anti-CD30 antibody),have been reported in NKTCL.Additionally,dacetuzumab and Campath-1 H have demonstrated promising results.Further encouraging data have been obtained using checkpoint inhibitors.The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL.Furthermore,anti-CCR4 monoclonal antibodies(m Abs)exert cytotoxic actions on both CCR4+tumor cells and regulatory T cells.Depletion of these cells and the long half-life of anti-CCR4 m Abs result in enhanced induction of antitumor effector T cells.The role of IL10 in NKTCL has also been investigated.It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies.Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission.Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease.The present review outlines the known immunotherapy targets for the treatment of NKTCL.

Distribution of natural killer cells and T-lymphocyte subsets in peripheral blood,gallbladder cancer and surrounding tissue

BACKGROUND: The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to define the relationship between the immune function of local cells and cancer development by investigating the distribution of natural killer (NK) cells and T-lymphocyte subsets in peripheral blood, the cancer tissue and the tissue surrounding gallbladder carcinoma. METHODS: The numbers of CD4(+) and CD8(+) T-lymphocytes and NK cells were measured by flow cytometry in samples taken from gallbladder cancer tissue, the surrounding tissues and peripheral blood of 38 patients, and compared with the numbers in the peripheral blood and gallbladder tissue of 30 patients with cholecystitis as controls. RESULTS: The numbers of CD4(+) and CD8(+) T-cells and NK cells in gallbladder cancer tissues were significantly higher than those in the surrounding tissue and gallbladder with gallstone. However, the ratio of CD4(+)/CD8(+) was lower in the cancer tissue than that in the surrounding tissue and tissue from gallbladders with gallstones. The distribution of CD4(+) and CD8(+) T-cells and NK cells in mucous membrane of cholecystitis gallbladder and that in the tissue surrounding gallbladder cancer were significantly different. CONCLUSIONS: Disproportionate and imbalanced distribution of NK cells and subsets of T-lymphocytes occurs in the mucous membrane proper of gallbladder cancer and surrounding tissue. Although gallbladder cancer tissue has higher expressions of CD4(+), CD8(+) and NK cells, the immune function is low or in an inhibited state. In gallbladder cancer immunization therapy, local cellular immunological function should be enhanced and the protective barrier improved.

Primary site and regional lymph nodeinvolvement are independent prognosticfactors for early？stage extranodal nasal？typenatural killer/T cell lymphoma

Background:Nasal-type extranodal natural killer/T-cell lymphoma(ENKTCL) originates primarily in the nasal cavity or extra-nasal sites within the upper aerodigestive tract.However,it is unclear whether the primary site can serve as an independent prognostic factor or whether the varying clinical outcomes observed with different primary sites can be attributed merely to their propensities of regional lymph node involvement.The aim of this study was to investigate the prognostic implications of the primary site and regional lymph node involvement in patients with early-stage nasal-type ENKTCL.Methods:To develop a nomogram,we reviewed the clinical data of 215 consecutively diagnosed patients with early-stage nasal-type ENKTCL who were treated in Sun Yat-sen University Cancer Center with chemotherapy and radiotherapy between 2000 and 2011.The predictive accuracy and discriminative ability of the nomogram were determined using a concordance index(C-index) and calibration curve.Results:The 5-year overall survival(OS) and progression-free survival(PFS) rates of patients with nasal ENKTCL were higher than those of patients with extra-nasal ENKTCL(OS:68.2%vs.46.0%,P = 0.030;PFS:53.4%vs.26.6%,P = 0.010).The 5-year OS and PFS rates of patients with Ann Arbor stage IE ENKTCL were higher than those of patients with Ann Arbor stage HE ENKTCL(OS:66.3%vs.59.2%,P = 0.003;PFS:51.4%vs.40.3%,P = 0.009).Multivariate analysis showed that age >60 years,ECOG performance status score >2,elevated lactate dehydrogenase(LDH) level,extranasal primary site,and regional lymph node involvement were significantly associated with lower 5-year OS rate;age >60 years,elevated LDH level,extra-nasal primary site,and regional lymph node involvement were significantly associated with lower 5-year PFS rate.The nomogram included the primary site and regional lymph node involvement based on multivariate analysis.The calibration curve showed good agreement between the predicted and actual 5-year OS and PFS rates,and the C-indexes of the nomogram for the OS and PFS rates were 0.697 and 0.634,respectively.Conclusions:The primary site and regional lymph node involvement are independent prognostic factors for earlystage ENKTCL treated with chemotherapy followed by definitive radiotherapy.

CD4+ T cells and natural killer cells: Biomarkers for hepatic fibrosis in human immunodeficiency virus/hepatitis C virus-coinfected patients

AIM To characterize peripheral blood natural killer(NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients.METHODS Peripheral mononuclear cells from 24 HIV/HCV(HBVnegative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: AntiCD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), antiNKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L(PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-Fas L(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using Flow Jo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained.RESULTS Samples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was(6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls(G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1(G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035).CONCLUSION Higher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage.

Inhibition effect of natural killer T cells on transplantation hepatocellular carcinoma in mice

Objective:The aim of this study was to investigate the inhibition effect of natural killer T(NKT) cells on transplantation hepatocellular carcinoma in mice.Methods:α-galactosylceramide(α-GalCer)-pulsed DC and Hep S were prepared as stimulus.Hepatoma xenograft model was established and mice were randomly divided into 4 groups(n=13 each group):(1) control group,intravenous injection of the same volume of saline.(2) mature DC group,intravenous injection of mature DC cells(4×106 cells).(3) α-GalCer-pulsed HepS group,intravenous injection of α-GalCer-pulsed HepS(4×106 cells).(4) α-GalCer-pulsed mature DC group,intravenous injection of α-GalCer-pulsed DC(4×106 cells).The changes of tumor volume in mice and survival period were measured every 2 days.Percentage of NKT cells in spleens and cytotoxicity of spleen cells were detected by flow cytometry.Tumor tissues were analyzed by histopathological examination.Results:In α-GalCer-pulsed Heps and DC groups,the average survival period was prolonged and tumor volume was markedly decreased,spleen cells and NKT cells were significantly increased,and tumor necrosis was evident,compared to the control group.Conclusion:α-GalCer-pulsed DC and HepS could activate NKT cells in vivo,also increase NKT cells cytotoxicity,inhibit the growth of hepatomas and prolong survival period.

Synchronous adenocarcinoma and extranodal natural killer/T-cell lymphoma of the colon:A case report and literature review

Extranodal natural killer/T-cell lymphoma(ENKTL) is a distinct subtype of non-Hodgkin's lymphoma and is rare in the colon.Synchronous adenocarcinoma and ENKTL of the colon has not been reported in the literature.In the present study,we report a 63-year-old male who suffered from intermittent bloody stools for 2 mo.He did not have fever,body weight loss or night sweat.Endoscopic and imaging studies revealed a 4.5-cm ulcerative mass in the ascending colon and a 3.0-cm polypoid,easy bleeding mass in the sigmoid colon,respectively.Thought to have double carcinoma of the colon,he received simultaneous right hemicolectomy and sigmoidectomy.The pathological diagnosis was a synchronous ENKTL(ascending colon) and adenocarcinoma(sigmoid colon).The literature on synchronous adenocarcinoma and malignant lymphoma of the colon was also reviewed.

Activation of natural killer T cells contributes to Th1 bias in the murine liver after 14 d of ethinylestradiol exposure

BACKGROUND As the main component of oral contraceptives(OCs),ethinylestradiol(EE)has been widely applied as a model drug to induce murine intrahepatic cholestasis.The clinical counterpart of EE-induced cholestasis includes women who are taking OCs,sex hormone replacement therapy,and susceptible pregnant women.Taking intrahepatic cholestasis of pregnancy(ICP)as an example,ICP consumes the medical system due to its high-risk fetal burden and the impotency of ursodeoxycholic acid in reducing adverse perinatal outcomes.AIM To explore the mechanisms and therapeutic strategies of EE-induced cholestasis based on the liver immune microenvironment.METHODS Male C57BL/6J mice or invariant natural killer T(iNKT)cell deficiency(Jα18-/-mice)were administered with EE(10 mg/kg,subcutaneous)for 14 d.RESULTS Both Th1 and Th2 cytokines produced by NKT cells increased in the liver skewing toward a Th1 bias.The expression of the chemokine/chemokine receptor Cxcr6/Cxcl16,toll-like receptors,Ras/Rad,and PI3K/Bad signaling was upregulated after EE administration.EE also influenced bile acid synthase Cyp7a1,Cyp8b1,and tight junctions ZO-1 and Occludin,which might be associated with EEinduced cholestasis.iNKT cell deficiency(Jα18-/-mice)robustly alleviated cholestatic liver damage and lowered the expression of the abovementioned signaling pathways.CONCLUSION Hepatic NKT cells play a pathogenic role in EE-induced intrahepatic cholestasis.Our research improves the understanding of intrahepatic cholestasis by revealing the hepatic immune microenvironment and also provides a potential clinical treatment by regulating iNKT cells.

Effects of Intraoperative Administration of Dexmedetomidine on the Percentage of T-Lymphocyte Subsets and Natural Killer Cells in Patients with Colorectal Cancer

Study Objective: To observe the effect of dexmedetomidine (DEX) on T-lymphocyte subsets and natural killer (NK) cells in the peripheral blood of perioperative patients with colorectal cancer. Design: A random double-blind control clinical study. Setting: A university hospital. Patients: Forty patients with colorectal cancer, ASA I-П. Interventions: All patients were randomly divided into a DEX group (n = 20) and a control group (n = 20). Before induction of anesthesia, epidural catheters were placed in the L1-L2 or T12-L1 intervertebral spaces. The DEX group received 1 μg/kg of DEX (200 μg/50 ml) intravenously for 15 min prior to the surgery, which was then infused at a rate of 0.5 μg/kg/h until 30 min before the end of the surgery. The control group received an intravenous infusion of saline (50 ml) instead of DEX during the same periods as the DEX group. All patients received routine anesthesia and postoperative analgesia. Measurements: Blood samples from all patients were collected at the following time points: before anesthesia (T0), 24 h after surgery (T1), 48 h after surgery (T2) and 72 h after surgery (T3). Changes in T-lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and NK cells were determined by flow cytometry. Main Results: Compared with the control group, the percentages of CD3+ and CD4+ cells and the CD4+/CD8+ ratio in the DEX group increased significantly from T1 to T3

Muscular involvement of extranodal natural killer/T cell lymphoma misdiagnosed as polymyositis: A case report and review of literature

BACKGROUND Natural killer(NK)/T cell lymphoma is a rare and highly aggressive malignant tumor,and is a special form of non-Hodgkin's lymphoma.Although extranodal involvement is frequently found in tissues such as the skin,testicular and gastrointestinal tract etc,its presence in skeletal muscle has scarcely been reported in the literature.CASE SUMMARY We report a case of extranodal NK/T cell lymphoma with muscle swelling as the first clinical manifestation.A 42-year-old man,who initially presented with localized swelling in the double lower extremities,demonstrated gradual facial and eyelid swelling,and his imaging results showed multiple sites of muscle damage throughout the body.The final pathological results suggested NK/T cell lymphoma,and immunohistochemistry showed CD20(-),CD3(+),CD30(+),CD56(-),EBER(+),Ki67(60%),TIA-1(+)and CD68(±)staining.The muscle swelling significantly improved after treatment with chemotherapy regimens.CONCLUSION This disease is difficult to diagnose and highly invasive,and should be included in the differential diagnosis of unexplained muscle swelling.

Prognostic role of ABO blood type in patients with extranodal natural killer/T cell lymphoma,nasal type:a triple.center study

Background:The prognostic significance of ABO blood type for lymphoma is largely unknown.We evaluated the prognostic role of ABO blood type in patients with extranodal natural killer(NK)/T-cell lymphoma(ENKTL).Methods:We retrospectively analyzed clinical data of 697 patients with newly diagnosed ENKTL from three cancer centers.The prognostic value of ABO blood type was evaluated using Kaplan-Meier curves and Cox proportional hazard models.The prognostic values of the International Prognostic Index(IPI) and the Korean Prognostic Index(KPI)were also evaluated.Results:Compared with patients with blood type O,those with blood type non-O tended to display elevated baseline serum C-reactive protein levels(P=0.038),lower rate of complete remission(P=0.005),shorter progression-free survival(PFS,P<0.001),and shorter overall survival(OS,P=0.001).Patients with blood type O/AB had longer PFS(P<0.001) and OS(P=0.001) compared with those with blood type A/B.Multivariate analysis demonstrated that age >60 years(P<0.001),mass ≥5 cm(P=0.001),stage Ⅲ/Ⅳ(P<0.001),elevated serum lactate dehydrogenase(LDH) levels(P=0.001),and blood type non-O were independent adverse predictors of OS(P=0.001).ABO blood type was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the intermediate-to-low-and high-to-intermediate-risk groups.Conclusions:ABO blood type was an independent predictor of clinical outcome for patients with ENKTL.

Extranodal natural killer/T-cell lymphoma(nasal type) presenting as a perianal abscess: A case report

BACKGROUND Extranodal natural killer(NK) T-cell lymphoma(ENKTL), nasal type is a rare subtype of extranodal non-Hodgkin lymphoma characterized by vascular damage and necrosis. The lesions usually present in the nasal cavity and adjacent tissues, however, the disease originates from the gastrointestinal or genitourinary tract in 25% of cases. Since rectal involvement in ENKTL is rare, rectal symptoms in the course of ENKTL are often misdiagnosed and considered to be related to benign diseases such as rectal fistula or perianal abscess.CASE SUMMARY We report the case of a 24-year-old Han Chinese female who initially presented with a perianal abscess that was subsequently diagnosed as nasal type ENKTL.Due to typical perianal pain, perianal abscess was diagnosed and surgical incision and drainage were performed. After recurrent, severe anal hemorrhages leading to hypovolemic shock and multiple surgeries, a diagnosis of ENKTL was made. The patient's condition gradually deteriorated, and she died shortly after initiation of chemotherapy.CONCLUSION Systemic and neoplastic diseases should be included in the differential diagnosis of any potentially benign perianal abscess complicated with recurrent hemorrhages.

The combined prognostic value of pretreatment neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio in stage IE/IIE extranodal natural killer/T-cell lymphoma

Objective This study aimed to explore the combined prognostic value of pretreatment neutrophil-tolymphocyte ratio(NLR), lymphocyte-to-monocyte ratio(LMR), and platelet-to-lymphocyte ratio(PLR) in newly diagnosed IE/IIE extranodal natural killer/T-cell lymphoma(ENKTL) treated with a P-Gemox regimen combined with radiotherapy or radiotherapy alone.Methods A total of 132 patients from 2009 to 2017 at the Sichuan Cancer Hospital were enrolled in the study. The cutoff values of NLR, LMR, and PLR using overall survival(OS) rate as an endpoint were obtained by the receiver operating curve. Results The cutoff value of NLR was 3.5. Patients with high NLR had significantly shorter progressionfree survival(PFS)(P < 0.001) and OS(P < 0.001) than those with low NLR. Similarly, the cutoff value of LMR was 3.0. The high LMR group had significantly longer PFS(P=0.001) and OS(P < 0.001) than the low LMR group. Similarly, the cutoff value of PLR was 191.7. The high PLR group was significantly associated with poor PFS(P < 0.001) and OS(P < 0.001) than the low PLR group. Furthermore, combining NLR, LMR, and PLR to build a new model to stratify patients into low-, intermediate-, intermediate-high-, and high-risk groups, there were also significant differences in PFS(P < 0.001) and OS(P < 0.001). The univariate analysis showed that presenting B symptoms, stage IIE, local tumor invasion, Eastern Cooperative Oncology Group score ≥ 2, elevated lactate dehydrogenase level, elevated NLR, decreased LMR, and elevated PLR were significantly associated with poor survival. The multivariate analysis demonstrated that PLR was an independent prognostic factor for both PFS(hazard ratio [HR]= 2.073, 95% confidence interval [CI]= 1.080–3.981, P = 0.028) and OS(HR = 2.127, 95% CI = 1.102–4.107, P = 0.025).Conclusion Elevated pretreatment PLR was a novel simple predictor of poor survival in patients with stage IE/IIE ENKTL. Combining NLR, LMR, and PLR could provide additional stratification.

Autologous Natural Killer Cell/Natural Killer T Cell Immunotherapy of Malignant Diseases

Adoptive immunotherapy, the therapeutic infusion of ex vivo activated cancer-fighting white blood cells that was pioneered by Dr. Steven Rosenberg over 30 years ago, has become more widespread due to outstanding published research documenting the clinical efficacy of this strategy. Based on the well-established in vivo functions of NK and NKT cells, their integral role in the efficacy of certain chemotherapeutic and immunomodulatory agents, and their direct therapeutic action as displayed in clinical trials, the use of autologous natural killer cell infusions is an appropriate and warranted therapeutic option for the treatment of malignant diseases, especially in patients whose disease is refractory to standard treatments such as chemotherapy and radiation.

Syndecan-1-coating of interleukin-17-producing natural killer T cells provides a specific method for their visualization and analysis

Natural killer T cells(NKT cells) are innate-like T cells that acquire effector functions while developing in the thymus, polarize into three distinct functional subsets viz. NKT1, NKT2 and NKT17 cells that produce interferon(IFN)-γ, interleukin(IL)-4 and IL-17, respectively. However, there has been no unique surface markers that define each subsets, forcing investigators to use intracellular staining of transcription factors and cytokines in combination of surface markers to distinguish among these subsets. Intracellular staining, however, causes apoptosis and prevents subsequent utilization of NKT cells in functional in vitro and in vivo assays that require viable cells. This limitation has significantly impeded understanding the specific properties of each subset and their interactions with each other. Therefore, there has been fervent efforts to find a specific markers for each NKT cell subset. We have recently identified that syndecan-1(SDC-1; CD138) as a specific surface marker of NKT17 cells. This discovery now allows visualization of NKT17 in situ and study of their peripheral tissue distribution, characteristics of their TCR and viable sorting for in vitro and in vivo analysis. In addition, it lays the ground working for investigating significance of SDC-1 expression on this particular subset in regulating their roles in host defense and glucose metabolism.