The preparation of blocking or antagonistic antibodies to CD40 can not only be used to detect the expression of CD40, but also to the treatment of inflammatory diseases or tumor immunotherapy. By using a recombinant CD40 protein, we generated fourteen hybridoma cell lines to produce CD40 antibodies. All the CD40 monoclonal antibodies could be used to detect the CD40 expression via western blotting, nine of which can also be used for FACS and one CD40 monoclonal antibody can block the CD40-CD40L interaction. Importantly, we got eight clones that produced agonistic antibodies to human CD40, while ten of the clones could activate the CD40 downstream gene expression of mouse splenocytes and seven of the clones could upregulate the expression of CD86 on mice B cells. Therefore, the CD40 monoclonal antibodies we generated can be used to test the expression of CD40, and to block or activate the CD40 signal.

糖基化修饰对单克隆抗体的结构、功能及药代动力学会产生影响。不同糖型结构通过与FcRs、Clq以及新生Fc受体(neonatal Fc receptor， FcRn)的结合而分别调节抗体依赖的细胞介导的细胞毒作用(antibody-dependent cytotoxicity， ADCC)、补体依赖的细胞毒作用(complement-dependent cytotoxicity， CDC)以及FcRn介导的药物消除半衰期。不同的细胞表达系统和细胞培养条件均会对糖基化的类型及程度产生影响，进而影响治疗性抗体的疗效以及安全性。通过糖基化工程可以控制特定糖型的形成，进一步优化单克隆抗体的效应功能和降低免疫原性。本文就单克隆抗体糖基化修饰研究进展进行综述。

代谢和免疫是机体生存最基本的需求。在长期的进化过程中，各种生物都形成了代谢和免疫反应的共同通路。因此，免疫反应和代谢调节高度统一，功能上相互依赖，这种免疫和代谢之间的相互作用可以被看作机体稳态调节的核心机制。代谢免疫学就在代谢和免疫相互联系的基础上研究免疫与代谢之间相互作用的途径、模式及其调控的一门新兴学科，并在此基础上更好地了解相关疾病的病理机制,探讨新的治疗方法。代谢免疫学的全新时代正在到来。

机体衰老过程中不仅免疫器官组织会发生相应的变化，免疫功能也会下降。T淋巴细胞是免疫系统的主要组成部分，不仅参与体液免疫，也参与细胞免疫。鉴于国内对T淋巴细胞增龄性变化研究较少，本文主要综述小鼠衰老过程中，不同月龄小鼠T淋巴细胞亚群的数量和功能的变化。整理发现，小鼠成年之后，CD4⁺T淋巴细胞在胸腺、外周血和脾脏中均发生增龄性的减少，CD8⁺T细胞则仅在胸腺中发生增龄性的减少，而在外周血和脾脏中发生增龄性的增加，但两者都会出现一定的功能障碍，其中包括增殖能力和免疫功能。

T细胞作为主要的免疫细胞在肿瘤发展和治疗的各个阶段发挥重要作用，而T细胞与肿瘤细胞共培养是建立T细胞与肿瘤细胞之间相互作用模型的重要途径。但是，有关T细胞与肿瘤细胞共培养方法存在一定难度并缺乏统一性，导致相关研究和应用发展缓慢。该综述主要概述并总结CD4⁺和CD8⁺T细胞与肿瘤细胞共培养的方法和应用。

TIL是从肿瘤组织中分离出的浸润性淋巴细胞。1986年Rosenberg研究组首先报道了在黑色素瘤患者的肿瘤组织中存在渗入性的淋巴细胞——TIL，这些细胞从瘤体中分离并经IL-2激活后可大量扩增，并对自身肿瘤有高度特异性杀伤活性。一般来说，TIL中绝大多数细胞是CD3⁺T细胞，不同肿瘤来源的TIL中，CD4⁺T细胞、CD8⁺T细胞的比例也有所差异，但大多数情况下以CD8⁺T细胞为主，其属于肿瘤过继免疫治疗中的高效效应细胞，其抗瘤效力相比LAK细胞强50～100倍。近年来，TIL的生物学表型及功能研究有了较大发展，这为TIL的临床应用带来了有利的价值，但目前国内外依然没有统一的培养技术规范。因此文章就目前TIL的研究进展以及各大实验室关于TIL的培养技术经验做一简要总结，以帮助基础科研及临床转化有效顺利地进行。

NK细胞作为固有免疫细胞，它的激活无MHC限制也不需预先致敏，其在肿瘤免疫治疗中的作用受到越来越多的关注。然而，在肿瘤发生过程中，肿瘤细胞依然可以逃避NK细胞的杀伤，相关机制也各有报道。为了解决此问题，近年来，在增强NK细胞抗肿瘤活性和提高NK细胞特异性杀伤肿瘤方面取得了令人瞩目的研究成果。这提示NK细胞在肿瘤免疫治疗中具有广阔的应用前景。本文主要对抗体介导的NK细胞、与受者杀伤细胞KIR不匹配的同种异体NK细胞、嵌合抗原受体介导的NK细胞和免疫检查点抑制剂联合NK细胞对肿瘤细胞的细胞毒活性进行归纳与总结，以期为后续肿瘤免疫治疗相关基础和临床应用研究提供较为清晰的思路和参考。

肿瘤细胞独特的有氧糖酵解代谢为其增殖生长提供能量，消耗了肿瘤微环境中的大量营养。肿瘤微环境中也存在大量的免疫细胞，免疫细胞活化、执行效应功能会发生与肿瘤细胞类似的代谢重编程现象，亦需要大量能量。因此免疫细胞与肿瘤细胞之间会存在激烈的代谢竞争，同时也存在密切的代谢调控。通过调整肿瘤代谢和免疫代谢的平衡，人为地抑制肿瘤代谢、增强免疫代谢，提高肿瘤内的免疫功能可能为肿瘤免疫治疗开辟一个新的方向。

免疫细胞代谢机制研究是免疫代谢研究的一个重要方向。免疫细胞在增殖、分化以及效应功能的执行等过程中会发生代谢重编程现象。本文综述了不同类型的免疫细胞静息或激活状态下的代谢通路。

To compare the transfection efficiency of cationic liposome lipofectamine3000 (Lipo3000) in different cell types, miRNA mimics with different concentrations were transfected into NIH3T3, EL4and CD4⁺T cells respectively by Lipo3000. The differences in transfection efficiency were compared by FACS among different types of cells and among different concentrations of miRNA mimics groups in the same types of cells. The results indicated that the highest transfection efficiency in NIH3T3 would be obtained when transfected with 100 nmol/L miRNA mimics by Lipo3000. For EL4 and CD4⁺T cells, the efficiency of transfection was improved with the increase of miRNA mimics concentration and could reach up to (12.13 ± 1.16)% and (3.80 ± 0.60%) respectively. It could be concluded that the transfection efficiency of Lipofectamine 3000 for adherent cells and suspension cells was significantly higher than that in primary cells.

放疗一直是恶性肿瘤的重要治疗手段之一，但是肿瘤的放疗抵抗却非常普遍，常常导致治疗失败。近几年来肿瘤免疫疗法进展迅速，免疫检查点抑制剂抗肿瘤效果令人瞩目。研究发现放疗联合应用免疫检查点抑制剂可产生抗肿瘤协同作用，甚至使对单一治疗抵抗的肿瘤转为对联合治疗敏感。本文对相关研究进行综述，为未来的临床应用提供思路。

中性粒细胞是人体重要的免疫细胞。近期发现其在肿瘤发生、发展中发挥一定作用，对其深入研究有利于肿瘤患者免疫状态评估，后者对肿瘤的免疫治疗和传统治疗均有指导意义。本文对近五年中性粒细胞的研究现状进行了整理，对其在肿瘤发生、发展中的作用作了较为全面的陈述。

We aimed to investigate the expression and role of activin A in patients with primary Sjogren's syndrome (pSS). 60 patients with pSS diagnosed in the Oral Mucosa Department of Shanghai Ninth People's Hospital， Shanghai Jiao Tong University School of Medicine and 30 controls were included. Serum levels of activin A were measured by ELISA. Expression of the activin A βA subunit, activin receptorⅠ(ACVRⅠ) A, ACVRⅡA, ACVRⅠB, ACVRⅡB and its signaling pathway-related molecules Smad2 and Smad3 in the PBMC of the patients and the healthy controls were analysed by real-time quantitative PCR. The expression of activin A in labial gland tissues was analysed by immunohistochemistry. The results indicated that activin A levels in the serum and labial gland tissues of pSS patients were significantly higher than those in the controls (P ＜ 0.05). Expression of activin A βA subunit in PBMC was significantly increased in the pSS patients(P ＜ 0.01), while ACVRⅠA and ACVRⅡA mRNA expressions in PBMC of the pSS patients were significantly decreased(P ＜ 0.05). There were no significant differences in the expression of ACVRⅠB, ACVRⅡB, Smad2 and Smad3 mRNA. Taken together, the abnormal expression of activin A in pSS patients implies that activin A might be involved in the pathogenesis of pSS.

Fas-FasL signaling pathway plays an important role in regulating the immune response, but its role in allergic inflammation is largely unknown. To study the effect of Fas-FasL signaling pathway on asthma pathogenesis, papain was used to establish the mouse acute asthma model. Infiltration of myeloid cells and T lymphocytes in lung tissues of wild type (WT) and Fas-deficient (Fas KO) mice was detected by flow cytometry. HE staining and PAS staining were used to detect the infiltration of inflammatory cells in lung tissues and the proliferation of goblet cells in asthmatic mice. The results showed that there was comparable distribution of eosinophils, neutrophils and monocytes in the alveolar lavage fluid and lung tissues between WT and Fas KO mice under the steady state. However, upon papain treatment, Fas KO mice had lower cell numbers of eosinophilic granulocytes, neutrophils, monocytes and goblet cells in lung tissues than those of WT mice, whereas the proportion of CD4⁺CD25⁺T cells was significantly increased. The above results reveal that the Fas signaling pathway could promote the infiltration of inflammatory cells in lung tissues in papain-induced asthma model. This study provides a new basis for exploring the role of Fas-FasL signaling pathway in the asthma models.

To investigate the phenotype and function of macrophages in systemic lupus erythematosus (SLE) patients and normal controls, CD14⁺ monocytes were isolated from the peripheral blood of SLE patients and healthy controls(HC) matched for age and sex. We cultured human monocytes for 7 days with macrophage colony-stimulating factor (M-CSF) to generate macrophages. The CD163 expression was detected by FACS. CD4⁺T cells were isolated from peripheral blood mononuclear cells (PBMC) of one healthy donor, and then were cocultured with macrophages from SLE or HC in a ratio of 5:1 with anti-CD3/CD28 stimulation for 4 days. The proliferation of T cells was detected by FACS. To determine the phagocytic activity of SLE macrophages, apoptotic cells were added into the cultures for 2 hours. The uptake of apoptotic cells was determined by FACS. Compared with HC macrophages, SLE macrophages exhibited lower expression of CD163. The immunomodulatory function of SLE macrophages was also impaired. SLE macrophages could not effectively suppress the proliferation of CD4⁺T cells. The phagocytic activity of SLE macrophages was deficient in engulfment of apoptotic cells. These findings suggest that SLE macrophages are deficient both in phenotype and function.

The bioinformatics was used to analyze the amino acid sequence of functional site of the Ricin B in Vibrio vulnificus VvhA, and the synthetic peptides were used to screen the naive human synthetic phagemid library Tomlinson I+J for specific single chain antibodies, which can lay the foundation for antibody treatment with blocking infection of Vibrio vulnificus. Three rounds of specific panning were performed through naive phage displayed human antibody libraries. One of the specifically identified anti-peptides scFv was named scFv-D2, the coding sequences of which belongs to human nucleotide sequence giving containing a VH fragment and a VL fragment. The clone named scFv-D2 clone was transformed into E.coli HB2151 for induced expression, and the binding activity of soluble scFv fragments with cytotoxic polypeptides was detected by ELISA. Our study showed that the scFv-D2 was isolated implied successfully to be screened from the Tomlinson I +J phagemid library and the soluble fragements had the meaningful affinity to VvhA peptides. Our work may lay the foundation for future studies involving blocking antibody therapy of the humanized antibody off against Vibrio vulnificus infection.

The assay for transposase-accessible chromatin using sequencing is a new epigenomic technique that detects the profiling of open chromatin landscape. To build a practicable method for human primary immune cells, conditions for cell lysis were tested. 0.1% NP-40 was the most appropriate condition that could lyse cells mildly but thoroughly. Tn5 transposases were used to cut off DNA and load sequencing adapters simultaneously. Following transposition step, library was prepared using PCR amplification. The distribution of insert fragment showed the interval of approximately 200 bp, which was analyzed with Agilent 2100 Bioanalyzer. Using bioinformatic tools to ensure the library quality, the total mapping rate was more than 94%, and mitochondrial DNA percentage was less than 38%, the signal of ATAC-seq was enriched at transcriptional start sites and the overlap between technical repetitions was approximately 80%. In conclusion, we made a high quality library evaluated multidimensionally and it is an ideal ATAC-seq method for processing human primary immune cells.

免疫缺陷和自身免疫被认为是免疫系统两种对立的状态，事实上两者密切相关。近几年许多文献报道了免疫缺陷患者合并自身免疫的情况，相比普通人群，免疫缺陷患者往往有更高的自身免疫风险。在临床上，原发性免疫缺陷患者常常合并风湿免疫表现，了解其临床表现的特点及发病机制，对于临床医师进行风湿免疫性疾病的诊断、治疗以及发现潜在的免疫缺陷有着重要的意义。

自体来源肿瘤全细胞疫苗（autologous whole tumor cell vaccine, AWTCV)是现今肿瘤免疫疗法中备受关注的一种靶向疗法，它利用患者自身来源的完整肿瘤细胞制备疫苗。与其他靶向特定抗原的免疫疗法相比，其具有携带相对完整的已知和未知肿瘤抗原、不受MHC限制等优势，因此避免了由于在肿瘤发展过程中某些抗原丢失而造成的肿瘤细胞免疫逃逸。不过，仅仅将肿瘤细胞灭活后制成的疫苗免疫原性极弱，并不能诱导足够的抗肿瘤免疫效应。为解决这一问题，目前研究者们主要采取对肿瘤细胞进行基因修饰，通过与佐剂或单克隆抗体联合使用等方法来达到提升疫苗抗肿瘤效果的目的。文章就AWTCV的制备、应用与发展前景作综述。

The aim of this study is to explore the correlation of clinical stages and the immune status with the level of myeloid-derived suppressor cells (MDSC) in the peripheral blood in patients with non-small cell lung cancer (NSCLC). Blood samples were collected from peripheral vein of 116 patients with NSCLC and 30 healthy volunteers. The ratios of MDSCs and Tregs in PBMC were detected by flow cytometry and the relationships with clinical stages, pathological types as well as the immunity were also researched. The results showed that compared with the healthy group, the rates of G-MDSC and M-MDSC in NSCLC were significant elevated (P<0.05); G-MDSC and pathological types were correlated with clinical stages (n=116, r=0.330, P<0.001; n=116, r=0.441, P<0.001). There was no correlation between the clinical stages and M-MDSC or Tregs (n=116, r=0.053, P=0.558; n=116, r=0.173, P=0.052). The G-MDSC correlated highly with Tregs (n=116, r=0.343, P<0.001), and so with the pathological types (r=0.333, P<0.001). The M-MDSC had no correlation with Tregs (r=0.333, P<0.001) or pathological types (r=-0.143, P=0.109).The level of MDSC in the peripheral blood of NSCLC patients was increased. Furthermore, G-MDSCs were found to have a positive correlation with clinical stages of NSCLC and Tregs. The results indicate that regulating the expression of MDSC may generate a new strategy for preventing occurrence of NSCLC and postoperative recurrence and metastasis [NCT02603003].

食物过敏发生率在逐年增加，尤其在儿童人群中。近年对食物过敏的治疗取得了很大的进展，食物过敏的治疗主要包括食物管理、过敏原特异性免疫治疗（allergen-specific immunotherapy， AIT）、辅助及替代治疗等。口腔免疫治疗是食物过敏研究中应用最多的过敏原特异性免疫治疗方法。辅助及替代治疗研究较多的是生物制剂、益生菌等膳食补充剂、中草药治疗、生命早期引入过敏食物等。文章就食物过敏的治疗进展作一综述。

Pyroptosis is a new research frontier and it plays key roles in inflammatory and immune response. Pyroptosis is involved in the development of a variety of diseases. This review summarizes the up-to-date research progress on the mechanisms of pyroptosis and pyroptosis-related diseases, providing a systematic and comprehensive overview of current knowledge in pyroptosis.

Agonistic anti-CD40 monoclonal antibodies (mAb) activate APC resulting in enhanced tumor antigen presentation and T cell response, which have been investigated as a potential anti-tumor immunotherapy for a long time. Recently coengagement of the Fc domain of agonistic anti-mCD40 mAb with FcγRⅡB is required for immune activation but there is little data showing how the activity of humanized anti-hCD40 mAb is regulated by FcγRⅡB. Here we show how FcγRⅡB regulates anti-hCD40 mAb activity. It was found that mutated hIgG1 constant region which has little FcγRs binding ability could not support agonistic anti-hCD40 mAb activity, and FcγRⅡB blocking antibody could significantly block the activity, furthermore hIgG1 constant region with enhanced FcγRⅡB binding could engage more potent agonistic activity. In addition, all three tested clones with different binding epitopes work in the same way, so agonistic anti-hCD40 mAb need FcγRⅡB engagement to exert anti-tumor activity while epitopes have little impact. What we have found provides clues to design better agonistic anti-hCD40 mAb.

To investigate the effect of Xinjiang black propolis on T cells in colon cancer rat model and its mechanism, 55 male Wistar rats were randomly divided into control group, model group, propolis prevention group, propolis treatment group and 5-FU group. Rat colon cancer model was established by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) enema. The treatment group was given corresponding drugs treatment for 30 days and the prevention group were given propolis by gavage just at the beginning of modeling. The body weight changes of rats were observed weekly, and the histopathological changes of colon cancer were observed by HE staining. The levels of serum cytokines TGF-βand IL-6 were detected by ELISA. The percentage of spleen T cells was detected by flow cytometry. The spleen tissue was examined by RT-PCR for the expression of transcription factors Foxp3 and ROR-γt mRNA. The results showed that compared with the model group, animal body weight of the propolis treatment group and the 5-FU group increased significantly after the treatment (P < 0.05). The number of Treg cells and the expression of the Foxp3 in the model group were significantly higher than those in the control group (P < 0.05). The number of Treg cells and the expression of Foxp3 in propolis prevention group and 5-FU group were significantly lower than those of the model group (P < 0.05). The number of Th17 cells and the level of ROR-γt in the model group were significantly higher than those in the control group (P < 0.05), but were significantly lower in the 5-FU group (P < 0.05). The ratio of Th17/Treg in the model group was significantly lower than that of the control group (P < 0.05), but was significantly higher in the 5-FU group than in the model group. Therefore, our study suggests Xinjiang black propolis may have a role in the prevention and treatment of colon cancer through regulating the function of related T cells and the expression of cytokines.

组织损伤后出现炎症反应不可避免。越来越多的证据显示炎症反应在皮肤损伤后内稳态的重建中至关重要，并且特异性的炎性细胞亚群及其分泌的细胞因子相互作用形成的网络直接影响角质形成细胞的增殖，进而影响组织修复。近年来发现皮肤中过度的炎症反应会延迟创伤愈合，而在创伤微环境作用下皮肤的角质形成细胞亦会加重炎症反应。因此深入了解组织修复时控制炎症反应的机制以及炎症反应怎样直接影响愈合过程非常重要。本文将对近期皮肤组织修复时控制炎症反应潜在的细胞及分子机制作一简要综述。

NG2⁺ glial cells constitute a major cell population in central nervous system (CNS), however, its role in neuroinflammation remains unclear. We used genetic approaches to specifically and partially deplete NG2⁺ glia in mouse CNS and subjected them to EAE (an animal model of multiple sclerosis) induction by active immunization or adoptive transfer of MOG_35-55-specific Th1/Th17 cells. While NG2⁺ glia promoted active-EAE and Th1-EAE, it protected mice from Th17-EAE. Our results thus suggest differential roles of NG2⁺ glia in Th1- and Th17-EAE, and provide potential therapeutic significance by modulating NG2⁺ glia in Th1- and Th17-EAE and multiple sclerosis.

金属元素在很多生命过程中都发挥重要的作用，是人体中必不可少的成分。许多金属元素在免疫系统中的应用已具有较长的历史。金属免疫学是研究金属离子及其化合物参与免疫细胞发育、免疫应答和免疫调控等过程的学科。金属免疫学这个概念的提出，使人们对金属元素在免疫学中的重要性有了更全面和深入的认识。近年来，许多关于金属元素在免疫系统中的功能的研究成果令人振奋。该文简述了锰、钙、铁和锌等几种常见金属元素在免疫系统中的功能，提出了锰作为危险相关分子模式（danger-associated molecular pattern, DAMP）或警报素的工作模型并阐述其作为天然免疫激动剂的实际应用，最后对金属免疫学的发展进行了展望。

To construct the luciferase reporter gene vectors containing human B7 homology 4 gene promoter sequence, three fragments of B7H4 gene promoter were amplified from genomic DNA of human peripheral blood mononuclear cells by PCR, then the fragments were cloned into pGL3-Basic luciferase reporter vector respectively. After sequencing analysis, the recombinant vectors and reference vector pRL-TK were transiently cotransfected into HEK-293T cells and dual-luciferase reporter gene system was used to test the activity of the promotors. The sequencing results showed the recombined plasmids containing different length B7H4 gene promoters (pGL3-hB7H4-2kb, pGL3-hB7H4-1kb and pGL3-hB7H4-0.5kb) were correctly constructed. The dual-luciferase reporter assay demonstrated that the recombinant vectors had the promoter activities in HEK-293T cells, and pGL3-hB7H4-0.5kb showed the highest transcription activity. In conclusion, the recombinant luciferase reporter vectors containing different length human B7H4 promoters were successfully constructed, providing a tool to investigate the transcriptional elements of human B7H4 promoter and identify the regulatory factors of B7H4 expression in tumor microenvironment.

自噬是真核生物对细胞应激物如错误折叠蛋白、长寿蛋白、受损的细胞器或胞内抗原进行降解的一种代谢途径。自噬与多种疾病相关，如神经退行性疾病、癌症等。现在发现，自噬与自身炎症性疾病（autoinflammatory disease， AUID）也存在较大关联。AUID是一类由遗传异质性因素引起的疾病，偶发性炎症、先天免疫反应失调等均会引起或加剧该类疾病的发生。已有研究表明，自噬通过对先天免疫信号传导途径的调控，可以对炎症水平进行控制。AUID相关的遗传变体可以直接激活炎症信号通路，而这些变体也可能造成自噬功能损伤，从而间接增加炎症反应水平。AUID中的遗传变体可以通过不同的机制对自噬造成损伤，文章就几种AUID中相关变体对自噬影响的反应途径及作用机制进行综述，以期为自噬作为治疗AUID的靶点提供新的策略。

We aimed to evaluate the effects of (5R)-5-hydroxytriptolide (LLDT-8) on NF-κB signaling pathway and its downstream signals of IL-6 and IL-8 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) induced by combination of TNF-α and IL-17. We used ELISA to measure the levels of IL-6 and IL-8 from supernatant of FLS culture. RT-PCR was applied to determine the messenger RNA expression of IL-6 and IL-8. Western blotting analysis was used to examine the expression of p-NF-κB p65 and p-IκBα in RA FLS. Immunofluorescence was utilized to study NF-κB p65 nuclear translocation of RA FLS. The results showed that: 1) LLDT-8was effective to inhibit the expression of IL-6 mRNA and IL-8 mRNA in RA FLS. It was also effective to inhibit the secretion of IL-6 and IL-8 in RA FLS. 2) LLDT-8 was effective to decrease the expression of p-IκBα and NF-κB p65 in RA FLS. 3) LLDT-8 was effective to significantly inhibit nuclear translocation of NF-κB p65. In conclusion, LLDT-8 could block NF-κB signaling pathway, resulting in the inhibition of IL-6 and IL-8 production in RA. Our results suggest that LLDT-8 could provide a new treatment possibility for RA patients.

复发性口腔溃疡是常见的口腔黏膜病，具有局限性、复发性、自愈性等特点。该病的发病原因至今不详，致病机制与治疗的研究一向备受关注。免疫功能异常在该病发生与复发过程中有着重要影响。近年来，大量研究提示细胞因子与该病的发生发展密切相关。本文对细胞因子在发病过程中所起的作用，以及在其治疗过程中的应用作一综述。

Both co-inhibitory and co-stimulatory pathways are critical for T cell activation, and antibodies that modulate these pathways are promising cancer therapeutic drug candidates. Indeed, blocking antibodies against PD-L1, PD-1 and CTLA-4 have achieved good results in some cancer patients. However, about 70% of patients do not respond well to these treatments. A lot of intrinsic mechanisms, especially low tumor mutation burden and limited tumor infiltrating lymphocytes contribute to the treatment resistance. To overcome these limitations, we designed an IFN-α/anti-PD-L1 fusion protein, which can simultaneously increase tumor infiltrating lymphocytes and block co-inhibitory PD-1-PD-L1 pathway. The IFN-α/anti-PD-L1 fusion protein showed T cell activating ability both in vitro and in vivo, which contributes to its potent anti-tumor activity in vivo. Taken together, our data indicate that IFN-α/anti-PD-L1 fusion protein may be a new strategy for cancer immunotherapy.

近年来，程序性死亡受体1（programmed death receptor 1， PD-1）/程序性死亡配体1（programmed death ligand 1， PD-L1）信号通路作为介导肿瘤免疫逃逸的重要途径而备受关注，抑制甚至阻断PD-1/PD-L1通路以增强T细胞毒性作用、提高机体免疫应答成为当下研究热点并取得了一系列突破性成果。目前，以PD-1/PD-L1抑制剂和CRISPR-Cas9技术靶向敲除PD-1/PD-L1基因为代表的免疫治疗策略已开始从实验室走向临床。与此同时，新的免疫治疗靶点的发现和治疗策略的组合将有助于更好地实现对PD-1/PD-L1信号通路的抑制作用，从而更有效地发挥此种免疫疗法在肿瘤治疗中的辅助作用。但目前阻断PD-1/PD-L1通路的免疫疗法仍存在适用人群有限、治疗效果相对欠佳等缺陷。此外，传统的肿瘤治疗评价标准对免疫疗法并不完全适用，新的标准亟待完善并规范化以用于临床疗效评价。本文将从PD-1/PD-L1信号通路出发，简明阐述其机制，并对当前研究成果进行全面介绍，同时聚焦国内外最新研究进展并对这一领域的发展趋势作出展望。

调节性固有淋巴样细胞（regulatory innate lymphoid cell， ILCreg）是ILC的一个亚群，通过分泌IL-10、TGF-β等细胞因子调控自身免疫病发生、发展，以维持免疫系统内环境稳定、抵抗病原菌和调控炎症。ILCreg在减轻过敏性肠炎、哮喘等自身免疫病中起到重要作用。文章将对ILCreg的发现及作用机制进行综述。

单倍型相合供者已经成为缺乏人类白细胞分化抗原（human leukocyte antigen， HLA）相合供者的移植候选患者的重要替代干细胞来源之一。然而，植入失败仍是单倍型相合移植、HLA不合无关供者和脐血移植后的主要并发症和死亡原因之一。近年来的研究发现，供者特异性抗HLA抗体（donor specific anti-HLA antibody， DSA）与HLA不合移植后的植入失败密切相关。了解DSA检测方法、流行病学以及处理手段对于减少植入失败、改善移植预后具有重要意义。

表达在APC表面的B7家族配体和T细胞表面的CD28家族受体是一对极为重要的共刺激分子。B7分子与CD28分子结合，作为第二信号调节T细胞的活性。以这2个家族分子作为靶点的肿瘤免疫治疗药物已经上市。糖基化是重要的蛋白质翻译后修饰方式，在细胞生长、发育、分化的各个阶段以及肿瘤的发生、发展过程中，对细胞和蛋白质功能的调节发挥着重要作用。文章对B7/CD28家族分子的糖基化研究进展情况进行综述。

越来越多的研究发现不协调的93同系物B1（uncoordinated 93 homolog B1， UNC93B1）在自身免疫性疾病的发生、发展中起重要作用。UNC93B1是一种内质网驻留蛋白，能够参与多种胞内TLR信号通路的激活、内质网钙电流的调节，促进机体自身免疫反应，增加炎性因子水平，对自身免疫性疾病的发生、发展具有重要意义。文章对UNC93B1对胞内TLR信号通路的影响及其在几种重要的自身免疫性疾病如SLE等发生、发展中的作用机制进行了系统的综述，可能为自身免疫性疾病提供新的治疗途径。

The joint cavity in patients suffered from RA has a characteristic hypoxic environment. In this study, we aimed to investigate the effect of fibroblast-like synoviocyte (FLS) on the polarization of macrophage to classically activated macrophage (M1) and alternatively activated macrophage(M2), and the role of macrophages in RA progression. Immunohistochemistry method was used to stain the characteristic surface markers CD197 and CD206 representing respectively M1 and M2 in the synovial tissue from RA and OA patients, and the number and proportion of M1 and M2 were analyzed. THP-1 cells were induced into M0 by PMA and then co-cultured with RA-FLS in the co-culture system, duplicates of Transwell system were placed in hypoxic and normoxic incubators respectively. Real-time PCR and immunofluorescence were used to detect the polarization of M0. The results showed that the numbers of M1 and M2 cells in the RA were higher than those in the OA, whereas the M1/M2 ratio was lower than that in the OA (P ＜ 0.05). After co-cultured with RA-FLS, the mRNA expression levels of the gene encoding M1 phenotype CCR7 and TNF-α were both increased while the expression levels of mRNA of M2 phenotype genes (IL-10, NOS-2 and TGF-β) were inhibited in 21% O₂ group (P ＜ 0.05). In 3% O₂ group, the mRNA expression levels of M1 and M2 phenotype genes in macrophages were both increased, the differences were statistically significant (P ＜ 0.05), and the results of immunofluorescence were consistent with those acquired from real-time PCR. In conclusion, our study shows that RA-FLS can promote activation of M2-type macrophage under hypoxic environment.

巨噬细胞是人体抵抗病原的第一道防线，在人体的免疫系统中发挥着重要作用，其在机体的新陈代谢、生长发育、组织修复以及稳态的维持等过程中也同样扮演着不可替代的角色，因此，巨噬细胞在靶向治疗多种疾病方面存在巨大潜力。同时，随着实验研究技术的不断发展，人类对于巨噬细胞的认识也得以发展，而这些研究成果将为巨噬细胞作为最具潜力的临床靶标的提供有效理论依据。故，对近年来不同组织定居巨噬细胞的起源和特异性发展，以及其在机体稳态和疾病时自我更新机制的研究进展，进行简单概述，将帮助我们全面了解巨噬细胞的功能特征，这对研究其在新陈代谢疾病、免疫疾病、组织修复、肿瘤及炎症等多种疾病的防治中作为治疗靶点具有重要意义，对人类抵抗疾病具有重大意义。