307例急性髓系白血病在WHO分型标准中的探讨

目的：通过对本组病例研究，提高对WHO分型诊断标准的认识。方法：选择2004-2005年在我院确诊的307例急性髓系白血病（AML），以形态学、免疫表型、融合基因等检测进行分析探讨。结果：按WHO分型诊断标准有14例原始细胞在20％～30％之间的患者被确诊为AML。免疫表型在髓系白血病中MPO、CD13、CD33表达最强，分别为96．77％、94．67％、91．53％。对M0的诊断有特异性，CD34、CD33达99％以上。融合基因检测：AML-M2b中90％以上AML1／ETO融合基因阳性，提示t（8；21）（q22；q22）易位。AML-M3中89．28％PML／RARα融合基因阳性，提示t（15；17）（q22；q12）易位。AML-M4EO中85％的CBFβ／MYH11融合基因阳性，提示inv（16）（p13；q22）。结论：WHO分型标准综合了传统的形态学分型，加入免疫学，融合基因等检测技术，结合临床特点等信息对AML进行分型，提高了对AML的诊断符合率。与FAB相比，更具有完全性、合理性、科学性，是AML分型的发展方向。     

SIRPγ-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling

Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγ^hi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγ^hi and SIRPγ^lo/– tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγ^hi cells serve as CSLCs and tumor immune checkpoint–initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.     

慢性前列腺炎细菌及免疫学研究

目的　了解慢性前列腺炎细菌感染情况 ,提高治疗水平。　方法　对 132例慢性前列腺炎患者行尿及前列腺液细菌五步培养法、药物敏感试验及前列腺液免疫球蛋白IgA和lgG测定 ,并根据药敏试验结果对部分患者进行治疗。　结果　前列腺液细菌培养阳性者 74例 ,其中金黄色葡萄球菌 32例 (耐药金黄色葡萄球菌 5例 ) ,表皮葡萄球菌 17例 ,大肠杆菌 10例 ,其它细菌 15例 ;细菌培养阴性者 5 8例。细菌培养阳性者前列腺液中IgG和IgA分别平均为 1.12 g/L和 0 .32 g/L(n =34 ) ,显著高于细菌培养阴性者 (0 .2 3g/L和 0 .0 2 g/L ,n =37;P =0 .0 31和P =0 .0 36 )。　结论　慢性前列腺炎患者前列腺液细菌培养阳性率较高 (5 6 .1% ) ,以革兰阳性菌多见 (6 6 .2 % ) ,细菌可能来源于女性生殖道。下尿路细菌定位诊断可简化为“两杯法”。前列腺液细菌培养阳性者的前列腺液中免疫球蛋白IgG和IgA水平较高     

Tim-3 mediates T cell trogocytosis to limit antitumor immunity

T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1–positive (PD-1⁺) Tim-3⁺CD8⁺ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis. Tim-3 blockade acted on Tim-3⁺ APCs in a PS-dependent fashion to disrupt the trogocytosis of activated tumor antigen–specific CD8⁺ T cells and PD-1⁺Tim-3⁺ CD8⁺ TILs isolated from patients with melanoma. Tim-3 and PD-1 blockades cooperated to disrupt trogocytosis of CD8⁺ TILs in 2 melanoma mouse models, decreasing tumor burden and prolonging survival. Deleting Tim-3 in dendritic cells but not in CD8⁺ T cells impeded the trogocytosis of CD8⁺ TILs in vivo. Trogocytosed CD8⁺ T cells presented tumor peptide–major histocompatibility complexes and became the target of fratricide T cell killing, which was reversed by Tim-3 blockade. Our findings have uncovered a mechanism Tim-3 uses to limit antitumor immunity.     

肝移植后供肝和宿主免疫学状态的变化

目的观察供肝免疫原性和宿主对供体抗原反应能力的动态改变。方法利用近交系LEW到WF的大鼠肝移植自发免疫耐受模型,取出不同时期的供肝,分别刺激长期生存的WF宿主,观察能否诱导出肝损害；另外对LEW→WF肝移植后不同时期的宿主,再次给予供体抗原刺激。结果(1)移植后第1、2天的同种移植肝,可激起长期生存的宿主出现暂时性肝损害(121±33、83±21),但第3天以后的则不能(28±9)。(2)给予供体同源的脾细胞刺激后,移植后7、14、28 d的宿主均未能诱导肝损害(56±17、66±11、61±35),但第56、84或112天的宿主均可被诱导出暂时性肝损害(98±25、158±43、330±82)。结论(1)肝移植后供肝的免疫原性在术后3 d基本消失。(2)移植术后1个月内宿主对供体抗原的刺激是处于低(无)反应状态的。     

Remodeling the tumor microenvironment via blockade of LAIR-1 and TGF-β signaling enables PD-L1–mediated tumor eradication

Collagens in the extracellular matrix (ECM) provide a physical barrier to tumor immune infiltration, while also acting as a ligand for immune inhibitory receptors. Transforming growth factor-β (TGF-β) is a key contributor to shaping the ECM by stimulating the production and remodeling of collagens. TGF-β activation signatures and collagen-rich environments have both been associated with T cell exclusion and lack of responses to immunotherapy. Here, we describe the effect of targeting collagens that signal through the inhibitory leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) in combination with blockade of TGF-β and programmed cell death ligand 1 (PD-L1). This approach remodeled the tumor collagenous matrix, enhanced tumor infiltration and activation of CD8⁺ T cells, and repolarized suppressive macrophage populations, resulting in high cure rates and long-term tumor-specific protection across murine models of colon and mammary carcinoma. The results highlight the advantage of direct targeting of ECM components in combination with immune checkpoint blockade therapy.     

感染后肠功能紊乱和树突状细胞的关系

目前感染后肠功能紊乱的免疫学发病机制仍不清楚,免疫细胞的激活可能会导致肠道动力和感觉功能的改变,其中重要的抗原提呈细胞如树突状细胞（dendritic cells,DC）在免疫细胞的激活中发挥着重要的作用。肠道组织中的树突状细胞可以激活初始和适应性免疫应答,产生Th1和Th2型细胞因子,这些细胞因子可以引起肠道神经肌肉功能的改变,从而使肠道功能发生紊乱。