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The role of the major histocompatibility complex (MHC) class I in prostate cancer therapy: A review

Nikoo Emtiazi Ehsan Zolfi Farhood Khaleghi Mehr Yasaman Moradi

Department of Pathology Medicine Rasool Akram Hospital School of Medicine Iran University of Medical Sciences Tehran IranDepartment of Urology School of Medicine Hasheminejad Kidney Center Iran University of Medical Sciences Tehran IranDepartment of Pathology School of Medicine Iran University of Medical Sciences Iran

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关键词： Major histocompatibility complex (MHC) class I Prostate cancer Treatment Immunotherapy Immune escape

摘要：

Cancers such as prostate cancer (PC) disproportionately impact middle-aged men (those between the ages of 45 and 60) and are a significant cause of male death worldwide. In treating PC, immunotherapy has a limited role despite its revolutionary impact on cancer care for many tumor types. Immune evasion, in which tumor cells evade detection and destruction by CD8 + cytotoxic T lymphocytes (CTLs), is an essential component in PC growth. Because of this lapse in immune monitoring, cancers can proliferate and disseminate. For CTLs to effectively recognize and eliminate tumor-associated antigens, stable and surface-localized expression of major histocompatibility complex class I (MHC-I) is critical. Furthermore, cancer cells often exhibit immune escape mechanisms that attempt to evade T-cell identification, such as reducing or eliminating tumor MHC-I expression. Immunotherapy for cancer, including the use of antibodies that target immunological checkpoint molecules, has a worse chance of success due to tumor immune escape. Another interesting finding is the presence of tumor-infiltrating cells in PC, which indicates that the immune system does not disregard PC. In this review, we reviewed its impact on different types of cancer and the ability of cancer cells to evade the immune system. We provided a brief overview of the MHC-I structure and its essential properties. Additionally, we have explored the function of MHC-I in PC treatment. Finally, we have reviewed emerging approaches to enhance anticancer vaccines and overcome MHC-I-mediated immune evasion in PC.

Understanding Human Leukocyte Antigens in Vascularized Composite Allotransplantation

Faisal A.A. Shurafa Kevin M. Klifto Stephen J. Kovach L. Scott Levin Saïd C. Azoury

Division of Plastic and Reconstructive Surgery Department of Surgery University of Missouri School of Medicine Columbia MissouriDivision of Plastic Surgery Department of Surgery University of Pennsylvania Perelman School of Medicine Philadelphia PennsylvaniaDepartment of Orthopedic Surgery University of Pennsylvania Perelman School of Medicine Philadelphia PennsylvaniaPenn Transplant Institute University of Pennsylvania Philadelphia Pennsylvania

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关键词： HLA Human leukocyte antigens Immune system Rejection Transplantation Vascularized composite allotransplantation

摘要：

Vascularized composite allotransplantation (VCA) has all the immunogenic risks of solid organ transplantation, while including the complexity and immunogenicity of the skin. This review provides an overview of the human leukocyte antigens (HLAs) system and its current role in VCA. HLA are cell surface glycoproteins critical for immune system surveillance. Their physiological function is to present self-recognized and foreign peptides to inhibit or initiate an immune response through induction, regulation of immune responses, and the selection of T-cells. The HLA system provides targets for stimulation during graft versus host disease, donor-specific HLA antibodies, and allograft rejection. HLA matching, identifying and using acceptable mismatches, and desensitization strategies may increase the immunologic compatibility of the HLA system between a donor and recipient in VCA.

牛冠状病毒N蛋白单克隆抗体的制备及鉴定

闫昭宇孔宁张琪许信刚单同领周宏超

西北农林科技大学动物医学院陕西杨陵712100中国农业科学院上海兽医研究所上海200000

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关键词： 单克隆抗体原核表达牛冠状病毒 N蛋白

摘要： 为了制备牛冠状病毒(Bovine coronavirus,BCoV)结构蛋白N的单克隆抗体,将N基因克隆到原核表达载体pCOLD I中,将构建好的重组质粒转化进大肠埃希氏菌BL21(DE3)中,诱导目的蛋白表达后纯化,用纯化的蛋白免疫小鼠制备杂交瘤细胞。对阳性杂交瘤细胞进行3次亚克隆后,用筛选鉴定正确的阳性杂交瘤细胞,腹腔注射小鼠制备腹水并进行初步纯化,利用Western blot检测腹水中抗体的特异性,利用间接免疫荧光试验(IFA)检测腹水中抗体的反应性。Western blot、IFA显示制备的腹水中抗体的特异性和反应性均良好。成功制备出一株能稳定分泌牛冠状病毒N蛋白单克隆抗体的杂交瘤细胞,为进一步研究牛冠状病毒和N蛋白的功能提供了材料。

Dose-dependent antiulcerogenic effect of bacterial levans on indomethacin-induced gastric lesions through modulation of NF-κB /TNF-α expression and apoptotic pathways

Heba Shawky Hanan A.A. Taie Sally A. El Awdan Asmaa Ezzat Amira A. Gamal Mona A. Esawy

Therapeutic Chemistry Department Pharmaceutical Industries and Drug Research Institute National Research Centre Dokki 12622 Cairo EgyptPlant Biochemistry Department Agricultural and Biological Research Institute National Research Centre Dokki 12622 Cairo EgyptPharmacology Department Medical Research Institute National Research Centre Dokki 12622 Cairo EgyptChemistry of Natural and Microbial Products Department Pharmaceutical Industries and Drug Research Institute National Research Centre Dokki 12622 Cairo Egypt

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关键词： Gastric ulcers Immunomodulation Levan NSAIDs Probiotics Ulcer healing

摘要：

Despite the availability of antiulcer agents, non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcers remain prevalent owing to poor tolerability and associated side effects. This study investigated the protective efficacy of bacterial levans against NSAID-induced gastric damage, evaluating their dose-dependent and molecular effects, and assessing possible synergy between LevAE and its probiotic-like producing isolate, Pseudomonas aeruginosa HI1. Levans were purified from different honey bacterial isolates and tested in Wistar rats receiving 100 mg/kg indomethacin for 10 days. All the treatments reduced the number and severity of ulcers in a dose-dependent manner. Notably, LevAE-Low showed superior gastroprotective effects, surpassing Ranitidine in reducing the ulcer burden, normalizing gastric inflammatory cytokines, alleviating oxidative stress, and preserving the mucosal structure. This superior effect was associated with NF-κB and BAX suppression; increased expression of COX-1, PGES, and Bcl-2; and restoration of the baseline BAX/Bcl-2 ratio. Interestingly, lower doses of LevAE and LevZ were more effective than higher doses, indicating a hormetic response, whereas LevP demonstrated a classical dose–response pattern. Although P. aeruginosa HI1 alone achieved comparable or superior cytokine and redox modulation, its combination with LevAE-Low showed weaker effects at some endpoints. These findings highlight the treatment- and dose-specific benefits of bacterial levans and probiotics in NSAID-induced gastric injury, emphasizing careful dose optimization to avoid undesirable outcomes.

Despite the availability of antiulcer agents, non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcers remain prevalent owing to poor tolerability and associated side ef

216例儿童急性淋巴细胞白血病转录组测序的单中心分析

王宇轩胡绍燕缪洁郭爱连何海龙

苏州大学附属儿童医院血液科 215000

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关键词： 急性淋巴细胞白血病转录组测序分子遗传学融合基因基因突变

摘要： 目的分析儿童急性淋巴细胞白血病(ALL)分子生物学特点,初步探索转录组测序(RNA-seq)技术在儿童ALL精准化治疗中的应用价值。方法回顾性分析216例初诊为ALL儿童的临床资料,所有患儿均经骨髓细胞形态学、流式免疫分型、逆转录聚合酶链式反应(RT-PCR)、荧光原位杂交(FISH)、染色体核型分析及RNA-seq检测确诊,采用多药联合化疗方案进行治疗,并进行随访。分析患儿基本信息、融合基因结果、基因突变情况;比较不同融合基因患儿的年龄、免疫分型、初诊WBC及不同融合基因治疗方案的微小残留病(MRD)缓解率。结果216例初诊ALL患儿中男性122例,女性94例,中位年龄4.8岁,其中132例(61.1%)患儿经RNA-seq检测出融合基因,共检测到73种融合基因。不同初诊年龄患儿的性别、初诊血常规、免疫分型比较无统计学差异(P>0.05)。RT-PCR、RNA-seq检测43种白血病融合基因结果的阳性率分别为35.65%(77/216)、37.96%(82/216),比较无统计学差异(χ^(2)=0.249,P=0.618>0.05)。FISH、RNA-seq检测3种基因重排结果的阳性率分别为30.09%(65/216)、31.02%(67/216),比较无统计学差异(χ^(2)=0.044,P=0.835>0.05)。将患儿在2例及以上的融合基因进行统计分析,在初诊ALL患儿年龄方面,绝大多数(93.7%)ETV6-RUNX1阳性患儿位于<10岁年龄段,6例(54.5%)BCR-ABL1、3例(100.0%)SIL-TAL1、2例(100.0%)GPBP1-GAPDH阳性患儿处于≥10岁年龄段。在免疫分型方面,48例(100.0%)ETV6-RUNX1阳性患儿全部表达B淋系抗原,3例(100.0%)SIL-TAL1阳性患儿全部表达T淋系抗原,2例(66.7%)MLLT10重排阳性患儿表达T淋系抗原,6例(66.7%)MTAP重排阳性患儿表达B淋系抗原,2例(100.0%)HOXA13重排阳性患儿全部表达T淋系抗原。在初诊WBC方面,TCF3-PBX1阳性患儿初诊时更倾向于高白细胞计数(WBC)(≥50×10^(9)/L)。初诊年龄<10岁及≥10岁的ETV6-RUNX1、BCR-ABL1、SIL-TAL1、GPBP1-GAPDH阳性患儿比较,有显著差异(P<0.05);急性B淋巴细胞白血病(B-ALL)及急性T淋巴细胞白血病(T-ALL)的ETV6-RUNX1、SIL-TAL1、MLLT10重排、MTAP重排、HOXA13重排阳性患儿比较,有显著差异(P<0.05);初诊WBC<50×10^(9)/L及WBC≥50×10^(9)/L的TCF3-PBX1阳性患儿比较,有显著差异(P<0.05)。202例采用CCCG-ALL2015/2020方案化疗的患儿进行化疗第19天评估点(D_(19))及化疗第46天骨穿评估点(D_(46))骨穿评估(注:3例诱导缓解疗程中死亡患儿未在规定时间点行骨穿评估),D_(19)MRD缓解率<0.01%为57.4%(116/202),D_(46)为94.5%(191/202)。不同融合基因治疗D_(19)的MRD缓解率<0.01%比较无统计学差异(P>0.05)。ph-like重排阳性患儿治疗D_(46)的MRD缓解率≥0.01%为33.33%,低于MRD缓解率<0.01%的66.67%,有显著差异(P<0.05)。7例采用CCLG-ALL2108方案化疗的患儿进行化疗第15天评估点(D_(15))及化疗第33天骨穿评估点(D_(33))骨穿评估,SIL-TAL1、HOXA1重排、MTAP重排阳性患儿的MRD缓解率均无统计学差异(P>0.05)。但值得注意的是,1例存在CDK6-HOXA13融合,D_(15)MRD转阴后在D_(33)评估时MRD很快转阳,另外1例存在MSI2-HOXA13基因的患儿D_(15)、D_(33)MRD均未转阴,但提示HOXA13重排阳性患儿诱导缓解反应疗效可能较差,需加强化疗。通过RNA-seq在120例患儿中检测到白血病相关基因突变,阳性率为55.6%(120/216)。其中变频率最高的前11位基因突变为:KRAS(10.6%,n=23)、NRAS(10.6%,n=23)、FLT3(8.7%,n=19)、NOTCH1(6.4%,n=14)、RUNX1(4.2%,n=9)、TP53(3.7%,n=8)、CREBBP(2.8%,n=6)、IKZF1(2.8%,n=6)、PTPN11(2.8%,n=6)、ATG2B(2.3%,n=5)、ETV6(2.3%,n=5)。B-ALL中突变频率最高的3位基因突变为:KRAS(10.2%,n=22)、NRAS(10.2%,n=22

Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists

Han Hee Lee Virginia Solitano Sujay Singh Ashwin N. Ananthakrishnan Vipul Jairath Gaurav Syal Brigid S. Boland Pradipta Ghosh John T. Chang Siddharth Singh

Division of Gastroenterology Department of Medicine University of California San Diego La Jolla CaliforniaDivision of Gastroenterology Department of Internal Medicine Yeouido St. Mary's Hospital College of Medicine Catholic University of Korea Seoul South KoreaDivision of Gastroenterology Department of Medicine Western University London Ontario CanadaDivision of Gastroenterology and Gastrointestinal Endoscopy IRCCS Ospedale San Raffaele Università Vita-Salute San Raffaele Milan ItalyCollege of Human Medicine Michigan State University East Lansing MichiganDivision of Gastroenterology Massachusetts General Hospital Boston MassachusettsHarvard Medical School Boston MassachusettsDepartment of Epidemiology and Biostatistics Western University London Ontario CanadaDepartment of Cellular and Molecular Medicine University of California San Diego La Jolla CaliforniaDepartment of Medicine Veterans Affairs San Diego Healthcare System San Diego CaliforniaDivision of Biomedical Informatics Department of Medicine University of California San Diego La Jolla California

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关键词： Upadacitinib biologics inflammatory bowel diseases infliximab risankizumab

摘要：

Background & Aims

We sought to ascertain how prior exposure to tumor necrosis factor (TNF) antagonists impacts treatment response with various classes of advanced therapies in patients with ulcerative colitis (UC), through a systematic review and meta-analysis.

Methods

Distribution of HLA Class I and II genetic profiles of Indian population: A regional analysis using 30,027 Umbilical cord blood samples

Sureka Rajendran Ambily Sivadas Kanaga Ganesan Georg Gutjahr Alagupandian Murugan Ankur Chaturvedi Nagaraja S Phani Chirayu Padhiar Prakash Sadashiv Gambhir

Molecular genetics Division Lifecell International Pvt Ltd Chennai Tamil Nadu IndiaSt. John’s Research Institute Bengaluru Karnataka IndiaDepartment of Health Science Amrita Institute of Medical Science and Research Center Amrita Vishwa Vidyapeetham Kochi Kerala IndiaLifecell West Regional Lab Pune Maharashtra India

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关键词： Allele frequency Cord blood bank HLA Haplotype frequency Hardy-Weinberg Equilibrium Indian population Linkage disequilibrium

摘要：

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells for treating life-threatening haematological disorders. India’s vast population, known for its cultural, linguistic, and genetic diversity, requires a significant need for HLA-matched donors. We analyzed HLA-A, −B, −C, −DRB1, and −DQB1 allele and haplotype diversity in 30,027 UCB units. Samples were categorized into six broad regional populations and further sub-clustered into nine groups based on the predominant language spoken. The most frequent haplotypes identified were A*33:03 ∼ B*44:03 ∼ C*07:06 ∼ DRB1*07:01 ∼ DQB1*02:02 (2.6 %), A*01:01 ∼ B*57:01 ∼ C*06:02 ∼ DRB1*07:01 ∼ DQB1*03:03 (2.4 %), and A*01:01 ∼ B*37:01 ∼ C*06:02 ∼ DRB1*10:01 ∼ DQB1*05:01 (1.4 %), showing significant inter-regional differences. We observed distinct allele distributions and high haplotype diversity, with the India South UCBB population displaying the highest number of unique haplotypes (63 %). Genetic distance analysis and multidimensional scaling revealed genetic relatedness between the regional and sub-regional populations. These findings offer key insights into Indian HLA diversity, inform donor recruitment strategies, enhance understanding of genetic relatedness to neighbouring populations, and highlight the need for population-specific repositories.

Pyoderma Gangrenosum: A Retrospective Study Comparing TNF-α Inhibitors with Ustekinumab

Howard Jie Yang William Spratt Francis Yi Xing Lai Senhong Lee

Department of Dermatology Monash Health Melbourne AustraliaMonash University Melbourne Australia

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关键词： Pyoderma gangrenosum Tumour Necrosis Factor-alpha retrospective cohort study ustekinumab

Corrigendum to “Preconditioning to mild oxidative stress mediates astroglial neuroprotection in an IL-10-dependent manner” [Brain Behav. Immun. 30 (2013) 176–185]

Niva Segev-Amzaleg Dorit Trudler Dan Frenkel

Department of Neurobiology George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv IsraelSagol School of Neuroscience George S. Wise Faculty of Life Sciences Tel Aviv University Tel Aviv Israel

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Targeting the adenosinergic axis in cancer immunotherapy: Insights into A 2A and A 2B receptors and novel clinical combination strategies

Iván Rodríguez-Pampín Lucía González-Pico Asier Selas Antonio Andújar Rubén Prieto-Díaz Eddy Sotelo

Center for Research in Biological Chemistry and Molecular Materials (CiQUS) University of Santiago de Compostela Santiago de Compostela SpainDepartment of Organic Chemistry Faculty of Pharmacy University of Santiago de Compostela Santiago de Compostela Spain

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PubMed期刊

关键词： A2AAR adenosine A2A receptor A2BAR adenosine A2B receptor ADO adenosine AR adenosine receptor Beff effector B cell Breg regulatory B cell BTK Bruton tyrosine kinase CAF cancer-associated fibroblast CAR chimeric antigen receptor CD39 ectonucleoside triphophate diphosphoydrolase 1 CD73 ecto-5′-nucleotidase CREB cAMP response element-binding protein CTL cytotoxic T lymphocyte CTLA-4 cytotoxic T lymphocyte-associated protein 4 DC dendritic cell HIF-1α hypoxia inducible factor 1α ICI immune checkpoint inhibitor IDO indoleamine 2,3-dioxygenase IL interleukin ITIM immunoreceptor tyrosine-based inhibitory motif MDSC myeloid-derived suppressor cell NF-κB nuclear factor κB NK natural killer PD-1 programmed cell death protein 1 PDE10 phosphodiesterase 10 PD-L1 programmed death-ligand 1 PKA protein kinase A RT radiotherapy SAR structure-activity relationship TAM tumor-associated macrophage Teff effector T cell TCR T-cell receptor TGF-β Transforming growth factor-β TIGIT T-cell immunoreceptor with Ig and ITIM domain TME tumor microenvironment TLR Toll-like receptor Treg regulatory T cell VEGF vascular endothelial growth factor

摘要：

The extracellular accumulation of adenosine is a central mechanism of immune evasion within the tumor microenvironment. Elevated adenosine levels—driven by hypoxia, chronic inflammation, and upregulated ectonucleotidase activity, primarily through ectonucleoside triphophate diphosphoydrolase 1 and ecto-5′-nucleotidase—induce profound immunosuppression and promote tumor progression. In this setting, adenosine acts mainly through 2 G protein–coupled receptors, the adenosine A_2A receptor (A_2AAR) and the adenosine A_2B receptor (A_2BAR), which modulate diverse immune and stromal cell populations. A_2AAR signaling suppresses the effector activity of cytotoxic T lymphocytes and natural killer cells, whereas A_2BAR activation exerts broader effects by amplifying myeloid-derived immunosuppression, driving stromal remodeling, and fostering angiogenesis and metastatic dissemination. This review provides a comprehensive overview of the distinct and converging roles of A_2AAR and A_2BAR in immune, stromal, and tumor compartments. We critically analyze current strategies for developing selective and dual A_2AAR/A_2BAR antagonists, with a focus on structure-activity relationships, scaffold optimization, and pharmacokinetic profiling. In addition, we examine ongoing clinical trials and emerging combination therapies involving A_2AAR and A_2BAR antagonists in conjunction with immune checkpoint inhibitors, adoptive cell therapies, enzymatic axis blockade, radiotherapy, and classical chemotherapy. We also underscore the therapeutic potential of dual A_2AAR/A_2BAR antagonists as a multitarget approach to counteract overlapping immunosuppressive mechanisms. Overall, targeting the adenosine axis—particularly through dual receptor blockade—represents a promising strategy for repro

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