Moxibustion regulates T-regulatory/T-helper 17 cell balance by modulating the microRNA-221/suppressor of cytokine signaling 3 axis in a mouse model of rheumatoid arthritis

Objective Rheumatoid arthritis(RA)progression is associated with the balance of T-regulatory(Treg)and T-helper 17(Th17)cells,while the role of microRNAs(miRs)in regulating Treg/Th17 cell balance has not been clarified.This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3(SOCS3)axis in the RA mouse model.Methods A mouse model of collagen-induced arthritis(CIA)was established in male DBA/1J mice.Twenty-two days after CIA induction,the mice received daily treatment with moxibustion for 12 times.Pathological scores were assessed according to the levels of synovial hyperplasia.The expression levels of cytokines interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay.The cluster of differentiation 4(CD4+)splenocytes was analyzed by fluorescence-activated cell sorting.The expression levels of RA-related miRs and target genes were subsequently detected,and the target of miR-221 was confirmed by the dual-luciferase reporter assay.Results It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β,IL-6,TNF-α,IFN-γand IL-17,while upregulated the expression level of IL-10.The Treg/Th17 cell balance was regulated by moxibustion treatment.The expression level of miR-221 was suppressed by moxibustion treatment.Furthermore,SOCS3 was found as the direct target of miR-221,which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.Conclusion Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.

Effect of T-regulatory cells and interleukin-35, interleukin-10, and transforming growth factor-beta on diffuse large B-cell lymphoma

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is an aggressive non-Hodgkin lymphoma that affects B lymphocytes.It can develop in the lymph nodes and can be localized or generalized.Despite DLBCL being considered potentially curable,little research has been conducted on the relationship between the body's immune response and DLBCL.AIM To study the expression and significance of T-regulatory cells(Tregs)interleukin(IL)-35,IL-10,and transforming growth factor-beta(TGF-β)in DLBCL.METHODS Data from 82 patients with DLBCL who were initially admitted to The First Affiliated Hospital of Ningbo University(Zhejiang Province,China)between January 2017 and June 2022 and treated with standard first-line regimens were reviewed.Three patients were lost to follow-up;thus,79 patients were included in the statistical analysis and then divided into three groups according to the evaluation of clinical efficacy:Incipient(new-onset and treatment-naïve),effectively treated,and relapsed-refractory.Thirty healthy individuals were included in the control group.The expression of peripheral blood T lymphocytes and their associated factors IL-35,IL-10,and TGF-βin the four groups were observed.RESULTS In contrast to the successfully treated and normal control groups,both the incipient and relapse-refractory groups exhibited greater proportions of CD4-positive(+)Tregs(P<0.05),whereas the proportion of CD8+Tregs did not differ substantially between the groups.Serum levels of IL-35 and IL-10 in the incipient and relapsed-refractory groups were higher than those in the effectively treated and normal control groups(P<0.05).There was no statistically significant distinction in the expression level of TGF-βbetween the groups(P>0.05).The correlation between IL-35 and IL-10 concentrations was significantly positive,with a correlation coefficient of 0.531(P<0.05).The correlation between IL-35 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.375(P<0.05).The correlation between IL-10 and TGF-βconcentration was significantly positive,with a correlation coefficient of 0.185(P<0.05).The expression concentrations of IL-35,IL-10 and TGF-βwere apparently and positively correlated(P<0.05).CONCLUSION Tregs IL-35,and IL-10 may be closely associated with the occurrence and development of DLBCL and the detection of related indices may be helpful in the analysis of disease prognosis.

5周递增负荷运动训练过程中T-helper1和T-helper2相关细胞因子基因表达的变化

目的:从辅助性T淋巴细胞(T-helper)细胞因子mRNA表达的角度探讨递增负荷运动下机体免疫机能变化的规律。方法:采用实时定量PCR检测技术,对进行5周递增负荷训练的健康男性受试者外周血单个核细胞的T-helper特征性细胞因子mRNA进行动态观察。结果:5周递增负荷运动训练过程中,训练组实验期间IL-2mRNA变化不明显,训练2、3和4周后IL-4mRNA明显升高,训练3周、4周、5周后IFN-γmRNA、IFN-γmRNA/IL-4mRNA、PFRmRNA明显高于实验前,训练5周后受试者最大摄氧量和PWC170明显提高。对照组IL-2mRNA、IL-4mRNA、IFN-γmRNA、PFRmRNA、有氧运动能力5周实验前后均无显著性差异。结论:5周递增负荷运动训练使T-helper1/T-helper2细胞因子基因表达上调,机体免疫平衡协调能力提高。

Effects of anesthetic methods on preserving anti-tumor T-helper polarization following hepatectomy

AIM:To investigate the impact of different anesthetic techniques on T-helper(Th) cell subsets in hepatocellular carcinoma(HCC) patients undergoing hepatectomy.METHODS:Sixty-one HCC patients who received hepatectomies were randomized into an epidural combined general anesthesia(G + E;n = 31) or a general anesthesia(G;n = 30) group.Blood samples were obtained the morning before the operation(d0),and on the second(d2) and seventh(d7) day after the operation.Th cell contents were evaluated using flow cytometry,realtime reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.RESULTS:In all 61 patients,Th1 and Th2 cell frequencies,and interferon-(IFN-) mRNA expression markedly increased on d2,compared to d0.They recovered slightly on d7,and the Th1/Th2 ratio increased markedly on d7,compared with d2.In contrast,Th17,regulatory T cell(Treg),and interleukin-17(IL-17) levels and FOXP3 mRNA expression showed no significant change on d2,and then markedly decreased on d7.Similarly,plasma IFN-concentration on d2 was much higher than that on d0,and then partly recovered on d7.As compared with the G group,in the G + E group,Th1 cell frequencies and the Th1/Th2 ratio were slightly higher on d2 and significantly higher on d7,while Th2,Th17,and Treg cell frequencies were slightly lower on d2,and significantly lower on d7.Consistently,on d7,IFN-mRNA and protein levels and the IFN-/IL-4 ratio in the G + E group were higher than those in the G group.In contrast,the IL-17 mRNA level,and IL-17 and transforming growth factor-1 concentrations in the G + E group were lower than those in the G group.CONCLUSION:G + E is superior to G in shifting the Th1/Th2 balance towards Th1,while decreasing Th17 and Treg,potentially benefiting HCC patients by promoting anti-tumor Th polarization.

Suppression of Allogeneic T Cells Proliferation by CD3/CD46-Induced T-regulatory 1 Cells

CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulatory 1 cell(Tr1)-specific cytokine phenotype in human CD4+ T cells.However,the role of CD46 as a co-stimulatory molecule in the modulation of the acquired immunity,such as transplant immunology,remains unclear.In this study,CD4+ T cells were isolated from human CD46-transgenic C57BL/6 mice by magnetic-activated cell sorting,and further induced by anti-CD3,anti-CD28 and anti-CD46 antibodies respectively,and anti-CD3/anti-CD28 antibodies,anti-CD3/anti-CD46 antibodies,or the monoclonal antibody panel against CD3/CD28/CD46.The levels of interleukin-2(IL-2),γ-interferon(γ-IFN),interleukin-10(IL-10) and transforming growth factor-β(TGF-β) were detected in the supernatants of different groups.Suppression of allogeneic T cell proliferation were assessed by using mixed lymphocyte reaction(MLR) assay,in which monoclonal antibodies against CD46 were added to the culture.The results showed that CD3/CD28,CD3/CD46 and CD3/CD28/CD46 co-stimulation could significantly induce stronger proliferation of T cells than CD3 stimulation(P<0.05),and CD3/CD28/CD46 co-stimulation significantly increased the proliferation of T cells when compared with CD3/CD28 or CD3/CD46 co-stimulation(P<0.05 for each).IL-2 and γ-IFN levels were much higher in CD3/CD28 co-stimulation group than in CD3,CD28,CD46 and CD3/CD46 groups(P<0.05 for each).IL-10 and TGF-β levels were dramatically increased in CD3/CD46 co-stimulation group as compared with those in the CD3,CD28,CD46 and CD3/CD28 groups(P<0.05 for each).CD3/CD46 co-stimulation significantly inhibited the T cell proliferation and allogenic immune responses through the secretion of IL-10 and TGF-β in MLR(P<0.05).These results suggested that CD3/CD46 can induce Tr1 cells to modulate allogenic immune responses,and it may become a novel target for the development of new therapeutic approach for T-cell-mediated diseases.CD46 plays an important role in regulating the T cell-mediated immune responses by bridging innate and acquired immunity.

Serum soluble suppression of tumorigenicity 2 as a novel inflammatory marker predicts the severity of acute pancreatitis

BACKGROUND Acute pancreatitis(AP)is an inflammatory disease in which the regulatory pathway is complex and not well understood.Soluble suppression of tumorigenicity 2(sST2)protein receptor functions as a decoy receptor for interleukin(IL)-33 to prevent IL-33/suppression of tumorigenicity 2L(ST2L)-pathwaymediated T helper(Th)2 immune responses.AIM To investigate the role of sST2 in AP.METHODS We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study.The serum levels of sST2,C-reactive protein(CRP)and Th1-and Th2-related cytokines,including interferon(IFN)-γ,tumor necrosis factor(TNF)-α,IL-2,IL-4,IL-5 and IL-13,were measured by highly sensitive ELISA,and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria.RESULTS Serum sST2 levels were significantly increased in AP patients,and further,these levels were significantly elevated in severe AP(SAP)patients compared to moderately severe AP(MSAP)and mild AP(MAP)patients.Logistic regression showed sST2 was a predictor of SAP[odds ratio(OR):1.003(1.001–1.006),P=0.000].sST2 cutoff point was 1190 pg/mL,and sST2 above this cutoff was associated with SAP.sST2 was also a predictor of any organ failure and mortality during AP[OR:1.006(1.003–1.009),P=0.000,OR:1.002(1.001–1.004),P=0.012,respectively].Additionally,the Th1-related cytokines IFN-γand TNF-αin the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups.CONCLUSION sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.

Immune mediators in the tumor microenvironment of prostate cancer

Prostate cancer tissue is composed of both cancer cells and host cells.The milieu of host components that compose the tumor is termed the tumor microenvironment(TME).Host cells can be those derived from the tissue in which the tumor originates(e.g.,fibroblasts and endothelial cells)or those recruited,through chemotactic or other factors,to the tumor(e.g.,circulating immune cells).Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor.Immune cells can have both anti-tumor and pro-tumor activity.In addition,crosstalk between prostate cancer cells and immune cells affects immune cell functions.In this review,we focus on immune cells and cytokines that contribute to tumor progression.We discuss T-regulatory and T helper17 cells and macrophages as key modulators in prostate cancer progression.In addition,we discuss the roles of interleukin-6 and receptor activator of nuclear factor kappa-B ligand in modulating prostate cancer progression.This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy.

Dynamic changes in the systemic immune responses of spinal cord injury model mice

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.

Ribavirin contributes to eradicate hepatitis C virus through polarization of T helper 1/2 cell balance into T helper 1 dominance

The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus(HCV) infection are reviewed.RBV up-regulates type 1 and/or 2 cytokines to modulate the T helper(Th) 1/2 cell balance to Th1 dominance.Examination of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells,which contributes to differentiating na?ve Th cells into Th2 cells while reducing their interleukin-10 production.The effects on T-regulatory(Treg) cells were also investigated,and RBV inhibited the differentiation of na?ve Th cells into adaptive Treg cells by downmodulating forkhead box-P3.These findings indicate that RBV mainly down-regulates the activity of Th2 cells,resulting in the maintenance of Th1 activity that contributes to abrogating HCV-infected hepatocytes.Although an interferon-free treatment regimen exhibits almost the same efficacy without serious complications,regimens with RBV will be still be used because of their ability to facilitate the cellular immune response,which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HCV.

Histopathology and immunophenotyping of late onset cutaneous manifestations of COVID-19 in elderly patients: Three case reports

BACKGROUND Several cutaneous manifestations such as urticarial rash,erythematous patches and chilblain-like lesions have been described in young adults with coronavirus disease 2019(COVID-19)and are present in up to 20%patients,but few reports exist describing histopathological and immunophenotypic characteristics of dermatological lesions in older patients.Our aim was to characterize skin lesions in elderly patients during late stages of COVID-19 from clinical,histological and immunophenotypic perspectives.CASE SUMMARY Three patients,admitted for COVID-19,and who developed cutaneous manifestations underwent skin biopsies.Immunophenotypic analysis for CD20,CD3,CD4 and CD8 was performed on skin biopsies to assess immune cell infiltrates.CD1a was used as a marker of Langerhans cells,and CD31 as a marker of endothelial cells.In the three study patients,cutaneous manifestations were evident in the late-stage of COVID-19(mean time from the first positive severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)swab to rash onset was 35 d).Skin biopsies showed a similar pattern of T lymphocyte infiltration in all patients.Indeed,a chronic dermatitis with perivascular lymphocytic infiltrate was observed with predominance of CD3+T-cell(CD3+).CONCLUSION Our study confirms previous reports.Histological and immunophenotypic patterns in our patients confirm results described in the two previous reported experiences.This pattern is similar to what is found in some lympho-proliferative disorders.Therefore,since these findings are non-specific,SARS-CoV-2 infection should be suspected.

Expression of T-Helper 17 Cells and Signal Transducers in Patients with Psoriasis Vulgaris of Blood-Heat Syndrome and Blood-Stasis Syndrome

Objective： To investigate the levels of cytokines related to T-helper （Th） 17 cells in serum and signal transducers in the psoriatic lesions of patients with psoriasis vulgaris of blood-heat syndrome （BHS） and blood-stasis syndrome （BSS）. Methods： Sixty patients with psoriasis vulgaris were divided into the BHS and BSS groups according to the syndrome differentiation of Chinese medicine （CM）. Ten healthy subjects were considered as the control group. Cytokine levels of interleukin （IL）-17, IL-23 and IL-6 in serum were determined by enzyme-linked immunosorbent assay. Expression levels of signal transducer and activator of transcription 3 （STAT3）, p38-mitogen-activated protein kinase （MAPK） and STAT6 in the psoriatic lesions were determined using immunohistochemistry （IHC）, Western blot, and real-time quantitative reverse transcription polymerase chain reaction, respectively. Results： Production of IL-17, IL-23 and IL-6 in the BHS group and BSS group were significantly increased compared with those in the control group （P〈0.05）. Levels of IL-17 and IL-23 in the BHS group were higher than those in the BSS group （P〈0.05）. Compared with the control group, IHC positive expressions and protein expressions of STAT3 and p38-MAPK, and the STAT3 mRNA expressions in the BHS and BSS groups were significantly higher （P〈0.05 or P〈0.01）. The protein expression of STAT3 in the BHS group was significantly higher than that in the BSS group （P〈0.05）. Conclusions： Cytokines in serum and signal transducers in the psoriatic lesions alter with various CM syndromes of psoriasis. The results provide scientific basis for the treatment based on syndrome differentiation of CM in treating psoriasis vulgaris.

Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment

During viral infection,immune cells coordinate the induction of inflammatory responses that clear infection and humoral responses that promote protection.CD4^(+)T-cell differentiation sits at the center of this axis.Differentiation toward T-helper 1(Th1)cells mediates inflammation and pathogen clearance,while T follicular helper(Tfh)cells facilitate germinal center(GC)reactions for the generation of high-affinity antibodies and immune memory.While Th1 and Tfh differentiation occurs in parallel,these CD4^(+)T-cell identities are mutually exclusive,and progression toward these ends is determined via the upregulation of T-bet and Bcl6,respectively.These lineage-defining transcription factors act in concert with multiple networks of transcriptional regulators that tip the T-bet and Bd6 axis in CD4^(+)T-cell progenitors to either a Th1 or Tfh fate.It is now clear that these transcriptional networks are guided by cytokine cues that are not only varied between distinct viral infections but also dynamically altered throughout the duration of infection.Thus,multiple intrinsic and extrinsic factors combine to specify the fate,plasticity,and function of Th1 and Tfh cells during infection.Here,we review the current information on the mode of action of the lineage-defining transcription factors Bcl6 and T-bet and how they act individually and in complex to govern CD4^(+)T-cell ontogeny.Furthermore,we outline the multifaceted transcriptional regulatory networks that act upstream and downstream of Bcl6 and T-bet to tip the differentiation equilibrium toward either a Tfh or Th1 fate and how these are impacted by dynamic inflammatory cues.

Association of T-helper cell cytokine level with age in patients with biliary atresia: a preliminary study

Background The pathogenesis of biliary atresia (BA) is associated with an inflammatory process involving the biliary tree. This study aimed to investigate the association of T-helper cell cytokine levels with age in patients with BA. Methods Twenty-eight patients with BA were divided into three groups according to their age (< 2 months, 2–3 months, and ≥ 3 months). All the patients underwent Kasai portoenterostomy. Blood samples were collected from the patients pre-operatively, and the liver tissue specimens were obtained during surgery. We detected serum levels of interleukin (IL)-1β, IL-12p70, interferon (IFN)-γ, IL-6, IL-10, and transforming growth factor (TGF)-β1 and liver expression of IL-1β, IL-6, and TGF-β1. Results The serum levels of IL-1β, IL-12p70, IL-6, and IL-10 in patients aged ≥ 3 months were significantly higher than those in patients aged < 2 months. There were no significant age-related differences in the IL-1β, IL-6 and TGF-β1 expres-sion levels in the liver tissue of patients with BA. Conclusions The serum levels of IL-1β, IL-6, IL-10 and IL-12p70 showed significant age-related differences in patients with BA. Interpretation of the role of cytokines in BA needs to take patient's age into consideration.

JAK inhibition ameliorated experimental autoimmune encephalomyelitis by blocking GM-CSF-driven inflammatory signature of monocytes

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system(CNS)due to the critical roles of these cells in the production of proinflammatory cytokines,differentiation of T-helper(Th)cells,and antigen presentation.The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling.However,the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis(MS)is unclear.Here,we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis(EAE),a model for MS.JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6^(Chi)monocytes and monocyte-derived dendritic cells in EAE mice.In parallel,the proportion of GM-CSF^(+)CD4^(+)T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition,which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage.Together,our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.

A T follicular helper cell origin for T regulatory type 1 cells

Chronic antigenic stimulation can trigger the differentiation of antigen-experienced CD4+T cells into T regulatory type 1(TR1)cells,a subset of interleukin-10-producing Treg cells that do not express FOxP3.The identities of the progenitor(s)and transcriptional regulators of this T-cell subset remain unclear.Here,we show that the peptide-major histocompatibility complex class Il(pMHCll)monospecific immunoregulatory T-cell pools that arise in vivo in different genetic backgrounds in response to pMHCll-coated nanoparticles(pMHCll-NPs)are invariably comprised of oligoclonal subpools of T follicular helper(TFH)and TR1 cells with a nearly identical clonotypic composition but different functional properties and transcription factor expression profles.Pseudotime analyses of scRNAseq data and multidimensional mass cytometry revealed progressive downregulation and upregulation of TFH and TR1 markers,respectively.Furthermore,pMHCIl-NPs trigger cognate TR1 cell formation in TFH cell-transfused immunodeficient hosts,and T-cell-specific deletion of Bcl6 or Irf4 blunts both the TFH expansion and TR1 formation induced by pMHCl-NPs.In contrast,deletion of Prdm1 selectively abrogates the TFH-to-TR1 conversion.Bcl6 and Prdm1 are also necessary for anti-CD3 mAbinduced TR1 formation.Thus,TFH cells can differentiate into TR1 cells in vivo,and BLIMP1 is a gatekeeper of this cellular reprogramming event.

Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts

Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion.CD81 cytotoxic T lymphocytes(CTLs)are involved in antigen-specific tumor destruction and CD41 T cells are essential for helping this CD81 T cell-dependent tumor eradication.Tumors often target and inhibit T-cell function to escape from immune surveillance.This dysfunction includes loss of effector and memory T cells,bias towards type 2 cytokines and expansion of T regulatory(Treg)cells.Curcumin has previously been shown to have antitumor activity and some research has addressed the immunoprotective potential of this plant-derived polyphenol in tumor-bearing hosts.Here we examined the role of curcumin in the prevention of tumor-induced dysfunction of T cell-based immune responses.We observed severe loss of both effector and memory T-cell populations,downregulation of type 1 and upregulation of type 2 immune responses and decreased proliferation of effector T cells in the presence of tumors.Curcumin,in turn,prevented this loss of T cells,expanded central memory T cell(TCM)/effector memory T cell(TEM)populations,reversed the type 2 immune bias and attenuated the tumor-induced inhibition of T-cell proliferation in tumor-bearing hosts.Further investigation revealed that tumor burden upregulated Treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor(TGF)-b and IL-10 in these cells.Curcumin,however,inhibited the suppressive activity of Treg cells by downregulating the production of TGF-b and IL-10 in these cells.More importantly,curcumin treatment enhanced the ability of effector T cells to kill cancer cells.Overall,our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses.