Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Adenosine 2A receptor contributes to the facilitation of postinfectious irritable bowel syndrome by γδ T cells via the PKA/CREB/NF-κB signaling pathway

BACKGROUND Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome(PI-IBS).γδT cells play a crucial role in innate and adaptive immunity.Adenosine receptors expressed on the surface ofγδT cells participate in intestinal inflammation and immunity regulation.AIM To investigate the role ofγδT cell regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS The PI-IBS mouse model has been established with Trichinella spiralis(T.spiralis)infection.The intestinal A2AR and A2AR inγδT cells were detected by immunohistochemistry,and the inflammatory cytokines were measured by western blot.The role of A2AR on the isolatedγδT cells,including proliferation,apoptosis,and cytokine production,were evaluated in vitro.Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction(RT-PCR).The animals were administered with A2AR agonist,or A2AR antagonist.Besides,γδT cells were also injected back into the animals,and the parameters described above were examined,as well as the clinical features.Furthermore,the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR.RESULTS PI-IBS mice exhibited elevated ATP content and A2AR expression(P<0.05),and suppression of A2AR enhanced PI-IBS clinical characteristics,indicated by the abdominal withdrawal reflex and colon transportation test.PI-IBS was associated with an increase in intestinal T cells,and cytokine levels of interleukin-1(IL-1),IL-6,IL-17A,and interferon-α(IFN-α).Also,γδT cells expressed A2AR in vitro and generated IL-1,IL-6,IL-17A,and IFN-α,which can be controlled by A2AR agonist and antagonist.Mechanistic studies demonstrated that the A2AR antagonist improved the function ofγδT cells through the PKA/CREB/NF-κB signaling pathway.CONCLUSION Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function ofγδT cells via the PKA/CREB/NF-κB signaling pathway.

ITP患者PD-1/PD-L1表达特点及其在Treg与Breg细胞之间的相互作用机制分析

目的探讨原发免疫性血小板减少症(ITP)患者细胞程序性死亡受体-1(PD-1)/细胞程序性死亡配体1(PD-L1)表达特点及其在调节性T细胞(Treg)、调节性B细胞(Breg)间的相互作用。方法选取2018年12月—2022年1月在我院治疗的ITP患者106例作为观察组,其中轻度患者32例,中度患者44例,重度患者30例。同时选取同期健康志愿者100例作为对照组。检测两组Treg细胞百分比、Breg细胞百分比、Treg细胞表面PD-1阳性率、Breg细胞表面PD-L1阳性率等,同时分析观察组不同病情程度患者各指标差异。结果观察组Breg细胞百分比、Treg细胞百分比、TGF-β、IL-10和IL-4水平均明显低于对照组(P<0.05);观察组Treg细胞表面PD-1阳性率、Breg细胞表面PD-L1阳性率、可溶性程序性细胞死亡蛋白-1(sPD-1)和IL-17水平均明显高于对照组(均P<0.05);两组可溶性程序性细胞死亡蛋白配体-1(sPD-L1)水平比较差异无统计学意义(P>0.05)。观察组重度患者Breg细胞百分比、Treg细胞百分比均明显低于轻度和中度患者(均P<0.05),而Treg细胞表面PD-1阳性率、Breg细胞表面PD-L1阳性率均明显高于轻度和中度患者(均P<0.05)。Treg细胞表面PD-1阳性率与Breg细胞表面PD-L1阳性率呈正相关(r=0.446,P<0.05)。观察组治疗后Breg细胞百分比、Treg细胞百分比、TGF-β、IL-10和IL-4水平有所升高(P<0.05),而Treg细胞表面PD-1阳性率、Breg细胞表面PD-L1阳性率、sPD-1和IL-17水平有所降低(P<0.05),治疗前后sPD-L1水平比较差异无统计学意义(P>0.05)。结论ITP患者Treg细胞表面PD-1和Breg细胞表面PD-L1阳性率明显升高,与患者病情严重程度呈正相关,同时Treg细胞表面PD-1和Breg细胞表面PD-L1表达之间存在相关性。

反复呼吸道感染患儿外周血单个核细胞中TLR2、TLR4表达情况与Th1/Th2免疫应答的关系

目的探讨反复呼吸道感染(RRTI)患儿外周血单个核细胞(PBMC)Toll样受体2(TLR2)、Toll样受体4(TLR4)表达情况与辅助性T细胞1(Th1)/辅助性T细胞2(Th2)免疫应答的关系。方法将2020年12月至2022年12月该院收治的65例确诊为RRTI的患儿纳入研究作为RRTI组。另选取同期于该院体检的健康儿童45例作为对照组。采用实时荧光定量PCR(qPCR)检测PBMC中TLR2和TLR4的信使核糖核酸(mRNA)相对表达水平。采用流式细胞仪检测PBMC中TLR2和TLR4蛋白表达率。采用酶联免疫吸附法(ELISA)检测血浆中Th1细胞因子干扰素-γ(IFN-γ)、Th2细胞因子白细胞介素-4(IL-4)水平及二者比值(IFN-γ/IL-4)。采用Pearson相关分析TLR2、TLR4蛋白表达率与血浆IFN-γ、IL-4水平的相关性。结果RRTI组血浆Th2细胞因子IL-4水平高于对照组,血浆Th1细胞因子IFN-γ水平低于对照组,IFN-γ/IL-4低于对照组,差异均有统计学意义(P<0.05)。RRTI组PBMC中TLR2和TLR4 mRNA相对表达水平及蛋白表达率均高于对照组,差异均有统计学意义(P<0.05)。Pearson相关分析显示,RRTI患儿PBMC中TLR2和TLR4蛋白表达率与血浆IFN-γ水平及IFN-γ/IL-4均呈负相关(P<0.05),与血浆IL-4水平均呈正相关(P<0.05)。结论RRTI患儿PBMC中TLR2、TLR4的表达及血浆Th1/Th2细胞因子均可能参与疾病的发生、发展的过程。过度活化的TLR2和TLR4可能会使Th1功能减弱、Th2功能增强。

CAR-T细胞治疗在儿童中的毒副作用

嵌合抗原受体(CAR)-T细胞因其特异性识别功能及细胞毒性,已成为治疗恶性肿瘤最有前途的方法之一,但它也具有一系列的毒副作用,特别是对儿童,毒性反应发展迅速,严重者还会危及生命。本文对CAR-T细胞治疗在儿童中的毒副作用,及其临床表现和治疗等方面进行概述,旨在优化其在儿童中的应用。

淋巴瘤患者行干细胞移植联合CD30嵌合抗原受体T细胞输注治疗的护理

目的 总结6例复发/难治性CD30阳性淋巴瘤患者进行自体干细胞移植联合抗CD30嵌合抗原受体T细胞输注治疗的护理经验。方法 对6例复发/难治性CD30阳性淋巴瘤患者,完善治疗前的护理评估,重点落实预处理毒性、细胞因子释放综合征以及植入综合征的护理,并将心理支持及健康教育纳入整个治疗过程。结果 6例患者均成功植入造血干细胞,外周血中检测到持续性CAR30转基因,其中5例完全缓解,1例部分缓解。5例出现细胞因子释放综合征,均为Ⅰ级,未观察到神经毒性。随访20.4(12.1,34.4)个月,患者均存活并保持其反应性。结论 自体干细胞移植联合抗CD30嵌合抗原受体T细胞输注治疗具有良好的耐受性和高度活性,护理在治疗各阶段以及毒副反应管理中发挥重要作用。

非剥脱点阵激光联合侧柏叶酊对斑秃小鼠IL-7/IL-7Rα信号通路和Tregs细胞亚群的影响

目的:研究1565 nm非剥脱点阵激光联合侧柏叶酊(Platycladus orientalis tincture,POT)对斑秃(Alopecia areata,AA)小鼠治疗作用以及对白细胞介素7(Interleukin 7,IL-7)/白细胞介素7受体α(Interleukin-7 receptorα,IL-7Rα)信号通路和调节性T细胞(Regulatory T cells,Tregs)亚群的影响。方法:将50只成年雄性C3H/HeJ小鼠随机分为对照组(C组),模型组[M组,环磷酰胺(Cyclophosphamide,CTX)诱导AA模型],M+1565 nm组(1565 nm非剥脱点阵激光治疗AA),M+POT组(POT治疗AA)、M+1565 nm+POT组(1565 nm非剥脱点阵激光联合POT治疗AA),每组10只。流式细胞术检测C组和M组皮损组织中Tregs细胞亚群的比例和所有组血液中单个核细胞中Tregs细胞亚群的比例。Western blot法检测各组小鼠皮损组织中IL-7和IL-7Rα的表达。结果:与C组比,M组皮肤组织IL-7和IL-7Rα的表达均明显增加,而且Tregs细胞比例明显减少(P<0.05)。与M组比,M+1565 nm组和M+POT组IL-7的表达均降低(P<0.05)。与M组比,M+1565 nm+POT组IL-7和IL-7Rα的表达均降低,且Tregs细胞比例都显著增加(P<0.05)。结论:1565 nm非剥脱点阵激光联合POT治疗可以抑制斑秃小鼠IL-7/IL-7Rα信号并减少Tregs细胞的比例。

CAR-T细胞免疫疗法在实体瘤中的研究进展

嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)成功治疗复发难治性白血病的历史已超过十年,如今,已有多款CAR-T细胞疗法获批用于治疗白血病和淋巴瘤等血液系统癌症,标志着免疫细胞治疗时代的到来。大量研究结果提示,CAR-T细胞疗法在实体瘤治疗领域同样充满潜力,但相关临床研究数据却不令人满意。CAR-T细胞疗法在实体瘤中面临靶抗原特异性不足、肿瘤物理屏障、异常代谢及免疫抑制性肿瘤微环境等多重不利因素,需要继续深入相关机制的研究,借助基因工程技术对CAR-T细胞进行改造,进一步提升其对实体瘤的疗效。本文就近年来CAR-T细胞疗法在实体瘤中的研究进展做一述评,探讨未来CAR-T细胞治疗的挑战和发展方向。

双靶点嵌合抗原受体-T细胞治疗复发难治多发性骨髓瘤患者疗效和安全性的Meta分析

背景嵌合抗原受体(CAR)-T细胞免疫疗法已在多发性骨髓瘤(MM)中取得较好的疗效,最常见的靶点为B细胞成熟抗原(BCMA)。单靶点CAR-T细胞免疫疗法的缺点是会导致疾病抵抗和复发,可能与抗原逃逸有关。为此,改进开发了双靶点CAR-T细胞治疗复发难治多发性骨髓瘤(RRMM),此方面尚缺乏系统的临床分析。目的对RRMM患者应用双靶点CAR-T细胞免疫疗法治疗的有效性及安全性进行Meta分析。方法计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普网7个数据库中有关双靶点CAR-T细胞治疗RRMM的单组率研究,检索时限为建库至2023-02-06。由2名研究人员使用自制的数据表单来提取收集数据,并采用非随机对照试验方法学评价指标进行文献质量评价。采用R Studio软件进行数据分析。结果共纳入9篇文献,包括200例既往接受过多线治疗的RRMM患者。双靶点CAR-T细胞疗法根据不同靶点可分为4类:BCMA+CD19、BCMA+CD38,BCMA+跨膜剂与钙调节亲环素配体的相互作用者(TACI)、BCMA+人信号淋巴细胞激活分子家族成员7(CS1),其中BCMA+CD19靶点的研究较多。根据输注形式不同CAR-T细胞疗法可分为4类:双特异性CAR-T细胞、联合或序贯输注两种不同CAR-T细胞、双顺反子结构、共转导。Meta分析显示,双靶点CAR-T细胞治疗RRMM的总缓解率(ORR)为90.0%(95%CI=0.849~0.943),完全缓解率(CRR)为54.6%(95%CI=0.416~0.673),微小残留病(MRD)阴性率为75.6%(95%CI=0.489~0.952),髓外病变(EMD)总缓解率为55.1%(95%CI=0.234~0.851),最后一次随访时的复发率为29.7%(95%CI=0.141~0.454),最后一次随访时的生存率为75.6%(95%CI=0.554~0.915),3~4级细胞释放因子综合征(CRS)发生率为16.4%(95%CI=0.094~0.245),神经毒性(ICANS)发生率为4.0%(95%CI=0~0.120)。敏感性分析提示结果稳定。Egger's检验结果显示,ORR(P=0.03)及EMD总缓解率(P=0.02)提示存在一定的偏倚风险;CRR(P=0.53)、MRD阴性率(P=0.79)、最后一次随访时的复发率(P=0.71)、生存率(P=0.98)、3~4级CRS发生率(P=0.90)、ICANS发生率(P=0.30)提示不存在发表偏倚。结论双靶点CAR-T细胞免疫治疗RRMM显示出良好的疗效和安全性,未来需要多中心、大样本、更长随访期的研究来进一步评估其疗效和安全性。

Donor-derived CD 19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD 19-positive B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation

Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.

CRISPR/Cas9敲除内源TCR增强TCR-T细胞对HPV16阳性宫颈癌SiHa细胞的杀伤

目的:基于CRISPR/Cas9基因编辑技术制备无内源TCR的TCR-T细胞并鉴定其在体外杀伤HPV16阳性宫颈癌SiHa细胞的功能。方法:培养健康志愿者外周血CD8^(+)T细胞和Jurkat细胞,CRISPR/Cas9基因编辑技术敲除CD8+T、Jurkat细胞的TCR基因,制备过表达转基因TCR的重组慢病毒,在敲除内源性TCR的CD8^(+)T和Jurkat细胞中用慢病毒过表达转基因TCR制备TCR-T细胞,多色FCM检测TCR-T细胞中TCR和CD3的表达水平,荧光素酶活性实验检测TCR-T细胞对HPV16阳性SiHa细胞的杀伤效率。结果:CRIPSR/Cas9基因编辑技术高效地敲除了外周血CD8^(+)T细胞和Jurkat细胞中的TRAC和TRBC基因,敲除效率分别为(81.4±4.5)%、(98.5±0.07)%,制备的无内源TCR的TCR-T细胞高效表达转基因TCR,在外周血CD8^(+)T和Jurkat细胞中表达率为(66.0±17.8)%、(97.3±2.6)%,敲除内源TRAC和TRBC基因有效增强CD8^(+)T和Jurkat细胞膜表达转基因TCR(均P<0.01),敲除内源TCR增强TCR-T细胞特异性杀伤HPV16阳性的SiHa细胞[(71.4±1.0)%vs(35.1±2.0)%,P<0.01)]。结论:无内源TCR的TCR-T细胞显著增强转基因TCR的表达和对HPV16阳性宫颈癌SiHa细胞的靶向杀伤能力,为提高TCR-T细胞的临床疗效提供了实验依据。

TCR-T免疫治疗肿瘤:现状、挑战及展望

T细胞受体工程T细胞(engineered T cell receptor-T cell,TCR-T)疗法和嵌合抗原受体T细胞(chimeric antigens receptor-T cell,CAR-T)疗法是目前过继性T细胞治疗最有效的两种方式。由于CAR仅能识别肿瘤表面的抗原,在实体瘤治疗中至今未有令人满意的结果。TCR不仅能识别肿瘤表面抗原,同时能识别胞内抗原,因此,TCR-T疗法在治疗实体瘤方面显示出前所未有的前景,成为极具潜力的治疗方式。本综述探讨了TCR-T疗法与CAR-T疗法识别癌症抗原机制的差异及当前TCR-T疗法靶向的临床靶点和不同类型的肿瘤抗原,描述了TCR-T抗肿瘤治疗的临床开发现状,并讨论了临床前评估TCR效价的标准和目前TCR-T治疗的优势、存在的局限性及可能有效的应对措施。最后,我们回顾了TCR-T治疗的现状和当前仍存在的一些挑战,强调靶向肿瘤特异性抗原的重要性,概述了结合检查点阻断治疗和溶瘤病毒等的新抗原特异性TCR-T治疗策略,以期这种联合治疗能够显著改善癌症的免疫治疗效果,并对未来TCR-T治疗根除多发性癌症提供一些思路。

T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo

T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus（EBV） associated malignancies.The EBV latent membrane protein 1（LMP1） is a 66-KD integral membrane protein encoded by EBV that consists of transmembrane-spanning loops.Previously,we have identified a functional signal chain variable fragment（scFv） that specifically recognizes LMP1 through phage library screening.Here,we constructed a LMP1 specific chimeric antigen receptor containing anti-LMP1 scFv,the CD28 signalling domain,and the CD3ζchain（HELA/CAR）.We tested its functional ability to target LMP1 positive nasopharyngeal carcinoma cells.HELA/CAR cells were efficiently generated using lentivirus vector encoding the LMP1-specific chimeric antigen receptor to infect activated human CD3＋ T cells.The HELA/CAR T cells displayed LMP1 specific cytolytic action and produced IFN-γ and IL-2 in response to nasopharyngeal carcinoma cells overexpressing LMP1.To demonstrate in vivo anti-tumor activity,we tested the HELA/CAR T cells in a xenograft model using an LMP1 overexpressing tumor.Intratumoral injection of anti-LMP1 HELA/CAR-T cells significantly reduced tumor growth in vivo.These results show that targeting LMP1 using HELA/CAR cells could represent an alternative therapeutic approach for patients with EBV-positive cancers.

基于TCR组库分析流程的非小细胞肺癌特征分析

目的·探究非小细胞肺癌(non-small cell lung cancer,NSCLC)免疫相关特征,发掘V-J基因中的肿瘤潜在标志物,为建立T细胞受体(T-cell receptor,TCR)-抗原识别预测模型提供基础。方法·收集704例NSCLC样本,用于构建一套系统的TCR组库分析流程,涵盖从原始数据到质控、过滤、TCR序列的识别和提取等上游分析部分,以及组库克隆分布、克隆分型、V-J基因共享性、互补决定区3(CDR3)分布特征以及克隆追踪等下游分析流程。使用Shannon-Weiner指数、Chao1等指数分析样本克隆分布。根据克隆扩增数目进行克隆分型,以探索不同分型间的差异。选取2例甲状腺乳头状癌(papillary thyroid carcinoma,PTC)样本进行去克隆扩增权重V-J基因共享分析,以探究低频克隆型对V-J基因共享性的影响。最后,通过分析V基因及高频克隆型CDR3分布特征和克隆追踪分析,监测肿瘤免疫前后克隆型频率的变化,寻找潜在的肿瘤标志物。结果·①NSCLC不同组织间克隆分布和克隆分型均存在显著差异,且在不同年龄与性别间存在显著差异。②在V-J基因共享性分析中发现了特定高共享V-J基因,同时在CDR3分布特征分析中存在非正态分布的高克隆V基因与氨基酸高频克隆型。③高频克隆型克隆追踪分析中,观察到NSCLC中高表达或新表达的高频克隆型,提示这些克隆型可作为潜在的肿瘤相关抗原或新抗原结合CDR3参考序列。④通过去克隆扩增权重V-J基因共享分析,发现原本低表达的TRBJ2-5基因表达频率显著增加,提示该基因可能为肿瘤免疫反应的潜在低频关键基因。结论·TRAV21和TRBV6.5基因在NSCLC中高克隆扩增,可作为潜在肿瘤标志物。

Focused evaluation of the roles of macrophages in chimeric antigen receptor (CAR) T cell therapy associated cytokine release syndrome

Cytokine release syndrome(CRS)is a major obstacle to the widespread clinical application of chimeric antigen receptor(CAR)T cell therapies.CRS can also be induced by infections(such as SARS-CoV-2),drugs(such as therapeutic antibodies),and some autoimmune diseases.Myeloid-derived macrophages play key roles in the pathogenesis of CRS,and participate in the production and release of the core CRS cytokines,including interleukin(IL)-1,IL-6,and interferon-γ.In this review,we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.

过继性T细胞疗法在头颈部鳞癌中的研究进展

过继性T细胞疗法(adoptive T cell therapy,ACT)是一种高度个性化的抗肿瘤治疗方法,临床研究正在迅速发展。研究表明,ACT疗法可以通过增加T细胞数量,增强对肿瘤组织的特异性和反应性,从而克服肿瘤免疫缺陷抑制的产生。ACT疗法目前有3种主要模式:肿瘤浸润淋巴细胞(TILs)、嵌合抗原受体T细胞(CAR-T)和T细胞受体工程化T细胞(TCR-T)治疗。本文对ACT疗法的分类及研究进展进行综述,包括TILs、CAR-T、TCR-T以及基于类器官共培养的过继性T淋巴细胞免疫治疗,探讨ACT作为头颈部鳞癌治疗方式的应用前景。

肺癌患者外周血和胸腔积液T细胞受体组库特征分析

目的 比较肺癌患者外周血和胸腔积液的T细胞受体(TCR)组库的免疫学特征。方法 收集2020年7月至2021年1月在复旦大学附属中山医院就诊的5例合并恶性胸腔积液肺癌患者的外周血和胸腔积液,分离外周血单个核细胞(PBMC)和胸腔积液单个核细胞(PEMC),提取基因组DNA,采用Illumina MiSeq平台对TCR进行高通量测序,分析TCR组库的多样性等特征。结果 PBMC和PEMC中的TCR克隆型、VJ pairs和互补决定区3(CDR3)序列的多样性和相关性差异均无统计学意义。PBMC中检测到的TCR克隆数量高于PEMC(P<0.05),VJ pairs和CDR3数量与PEMC差异无统计学意义。PBMC和PEMC配对样本的共有VJ pairs数量占总VJ pairs的比例高于共有克隆型和CDR3序列的数量比例(P<0.05),后两者差异无统计学意义。PEMC中高扩增克隆(HEC)数量和占比均高于PBMC。同时鉴定了36个在PBMC和PEMC中差异表达的VJ pairs,其中25个在PEMC中表达升高、9个在PEMC中表达降低。结论 肺癌患者外周血和胸腔积液的TCR组库表现出不同的特征性变化,可能为肺癌重要的免疫病理学特征。

Pien Tze Huang alleviates Concanavalin A-induced autoimmune hepatitis by regulating intestinal microbiota and memory regulatory T cells

BACKGROUND Traditional Chinese medicine has used the drug Pien Tze Huang(PTH),a classic prescription,to treat autoimmune hepatitis(AIH).However,the precise mode of action is still unknown.AIM To investigate the mechanism of PTH in an AIH mouse model by determining the changes in gut microbiota structure and memory regulatory T(mTreg)cells functional levels.METHODS Following induction of the AIH mouse model induced by Concanavalin A(Con A),prophylactic administration of PTH was given for 10 d.The levels of mTreg cells were measured by flow cytometry,and intestinal microbiota was analyzed by 16S rRNA analysis,while western blotting was used to identify activation of the toll-like receptor(TLR)2,TLR4/nuclear factor-κB(NF-κB),and CXCL16/CXCR6 signaling pathways.RESULTS In the liver of mice with AIH,PTH relieved the pathological damage and reduced the numbers of T helper type 17 cells and interferon-γ,tumor necrosis factor-alpha,interleukin(IL)-1β,IL-2,IL-6,and IL-21 expression.Simultaneously,PTH stimulated the abundance of helpful bacteria,promoted activation of the TLR2 signal,which may enhance Treg/mTreg cells quantity to produce IL-10,and suppressed activation of the TLR4/NF-κB and CXCL16/CXCR6 signaling pathways.CONCLUSION PTH regulates intestinal microbiota balance and restores mTreg cells to alleviate experimental AIH,which is closely related to the TLR/CXCL16/CXCR6/NF-κB signaling pathway.

CAR-T细胞治疗复发难治性弥漫大B细胞淋巴瘤1例报告并文献复习

1例复发难治性弥漫大B细胞淋巴瘤(R/RDLBCL)患者在接受多线治疗后,疾病仍进展,后采用嵌合抗原受体T细胞(CAR-T)治疗。该患者在输注CAR-T细胞后第1天出现3级细胞因子释放综合征,经治疗后缓解,目前处于部分缓解状态。证实CAR-T可被视为治疗R/RDLBCL的有效选择。

Distinct toll-like receptor expression in monocytes and T cells in chronic HCV infection

瞄准：丙肝病毒经常建立长期的感染。最近的研究建议病毒、细菌的感染在与控制相比的感染 HCV 的病人是更普通的。病原体被像使用费的受体(TLR ) 认出塑造适应、天生的有免疫力的回答。方法：在这研究，估计感染 HCV 的主人的能力认识到入侵病原体，我们调查了像使用费的受体表示在天生(单核白血球) 并且适应(T 房间) 由即时 PCR 的有免疫力的房间。结果：我们决定 RNA 为 TLR 铺平 2， 6。7， 8， 9 和 10 个 mRNA 层次起来与控制相比在感染 HCV 的病人在单核白血球和 T 房间调整了。TLR4 在 T 淋巴细胞在仅仅上面被调整，当 TLR5 有选择地在感染 HCV 的病人的单核白血球被增加时。MD-2， TLR4 合作受体，当 CD14 和 MyD88 仅仅在单核白血球被增加时，在病人的单核白血球和 T 房间被增加。结论：我们的数据在多半在感染 HCV 的个人联系到病原体和有免疫力的防卫的天生的识别的 TLR 表示上披露新奇详情。