Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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Atypical cutaneous γδ T cell proliferation with morphologic features of lymphoma but with clinical features and course of PLEVA or lymphomatoid papulosis

Reactive lymphoid infiltrates of the skin composed predominantly of gamma‐delta (γδ) T cells are not well described in the literature. Herein we report a case of an otherwise healthy 4‐year‐old male who presented with a waxing and waning papular rash characterized by small, discrete crusted papules spread across his trunk, face and extremities. Clinical evaluation revealed no evidence of systemic disease. Microscopic examination revealed a dermal, perivascular infiltrate of highly atypical lymphocytes with a γδ T cell phenotype, worrisome for primary cutaneous γδ T cell lymphoma. The clinical course, however, was that of a reactive condition and prompted consideration of a diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP). In many ways, this case defies current classification schemes and seems to expand the spectrum of reactive γδ T cell infiltrates of the skin.     

抗PD-(L)1、抗CTLA-4免疫治疗标志物研究进展

免疫检查点抑制剂已经改变了包括肺癌、黑色素瘤等许多肿瘤的治疗情况，并且在一些难治性肿瘤中表现出持久的应答率，然而在部分接受治疗的患者中表现出无反应及严重免疫相关副作用。为了优化免疫疗法的使用，可能需要多种临床应答的预测性标志物。本研究回顾了几种潜在有效生物标志物的可用数据，通过免疫组化检测肿瘤细胞和免疫细胞中PD-L1的表达，提示其是一种临床疗效的良好预测标志物;且PD-L1表达阴性者经免疫治疗后仍可获益。PD-L1表达在肿瘤内是动态和异质性的:在原发性灶和转移灶之间或在穿刺标本和大体标本之间表达不一致。肿瘤突变负荷与新抗原的高比率可获得持久获益。外周血标志物也可作为潜在标志物，增加的绝对淋巴细胞计数（ALC）与疾病控制和生存显著相关。在这篇综述中，我们旨在讨论抗PD-（L）1与抗CTLA-4 免疫治疗相关标志物研究现状，为临床运用提供指导，以便能够准确筛选出从这些治疗中获益更多的患者。     

脾保留手术治疗创伤性脾破裂的临床探讨

目的：分析脾保留手术治疗创伤性脾破裂的疗效。方法选取该院2011年6月—2014年6月收治的创伤性脾破裂患者，共计56例，分为两组，各28例，对照组进行脾切除手术，研究组进行脾保留手术。结果研究组临床有效率为92.86%，对照组临床有效率为78.57%；术后并发症发生率研究组为10.71%、对照组为28.57%。结论脾保留手术治疗创伤性脾破裂的疗效显著，恢复快，并发症少，在患者伤情允许情况下优先选择脾保留术。     

The prognostic role of tumour‐infiltrating lymphocytes in oral squamous cell carcinoma: A meta‐analysis

It has been suggested that tumour‐infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta‐analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta‐analysis. Our pooled meta‐analysis showed that high infiltration of CD8⁺ TILs, CD45RO⁺ TILs and CD57⁺ TILs favoured better overall survival (OS). However, high infiltration of CD68⁺ macrophages and CD163⁺ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8⁺ TILs, CD45RO⁺ TILs, CD57⁺ TILs, CD68⁺ macrophages and CD163⁺ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.     

脑肿瘤患者手术前后T细胞亚群及NK细胞活性的变化

目的 探讨脑肿瘤患者手术前后细胞免疫功能的变化及其临床意义。方法 采用单克隆抗体酶标法对22例脑肿瘤和12例脑内血肿患者手术前后不同时期的T细胞亚群及NK细胞活性进行动态监测。结果 脑肿瘤CD3^ 、CD4^ ,CD10^16 56和CD4^ /CD8^ 比值较对照组均有不同程度降低。而胶质瘤组较其余两组明显下降。34例患者术后4期CD3^ ,CD4^ ,CD16 56^ 比值均发生变化。胶质瘤组在术后1至2周明显低于其余两组。术后3至4周才逐渐恢复至正常水平。结论 脑肿瘤患者细胞免疫功能被抑制。且恶性胶质瘤较良性肿瘤更为明显，手术应激能导致T细胞亚群及NK细胞活性变化。脑肿瘤切除术后细胞免疫功能呈现暂时抑制至逐渐恢复的过程。     

树突状细胞激活的肿瘤浸润性淋巴细胞体外对自体肝癌细胞杀伤活性的研究

目的探讨树突状细胞(DC)激活的肿瘤浸润性淋巴细胞(TIL)体外对自体肝癌细胞杀伤活性.方法从肝癌患者外周血获取DC,应用粒/巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4)和肿瘤抗原激活DC,然后用DC来激活TIL,观察TIL在体外对自体肝癌细胞的杀伤活性.结果DC激活的TIL具有很高的对自体肝癌细胞杀伤活性,杀伤率为(89.39±3.05)%,明显高于未经DC激活的TIL、CD激活的T淋巴细胞和未经DC激活的T淋巴细胞对自体肝癌细胞的杀伤率.结论肝癌患者外周血DC能诱导TIL产生高效而特异的抗肝癌免疫.     

On the Role of Proteasomes in Cell Biology and Proteasome Inhibition as a Novel Frontier in the Development of Immunosuppressants

The proteasome, a large protease complex in cells, is the major machinery for protein degradation. It was previously considered a humble garbage collector, performing housekeeping duties to remove misfolded or spent proteins. Until recently, the interests of immunologists in proteasomes were focused largely on its role in antigen processing. Its real importance in cell biology has only been revealed contemporarily due to the availability of relatively specific inhibitors. It has now become increasingly clear that many aspects of immune responses highly depend on proper proteasome activity. Recently, a proteasome inhibitor has been successfully used to prevent acute as well as ongoing heart allograft rejection in mice. Such inhibitors are also efficacious in treating several autoimmune diseases, such as arthritis, psoriasis, and probably type I diabetes, in animal models. Phase II and III clinical trials of proteasome inhibitors in treating various tumors have shown promising results, and the side-effects of these drugs are tolerable. Therefore, proteasome inhibition represents a new and promising frontier in immunosuppressant development.     

小肠浆肌膜腔内自体脾组织移植动物模型的建立与意义

目的探讨增加自体脾组织移植量的方法,提高自体移植脾组织的功能。方法贵州小型香猪3头,经肌注麻醉后剖腹切除脾脏,取脾脏的1/2约150g,切成1mm×1mm×1mm小块备用。在距Treitz韧带50cm处,切取保留肠系膜血管的空肠30cm旷置,再吻合肠管恢复肠腔通道,缝闭肠系膜裂口。旷置空肠等分2段,去除肠粘膜,缝闭一端,将约50g脾组织块分别植于2段肠浆肌膜腔内,缝闭另一端口,妥善固定于肠系膜上。大网膜内移植30g脾组织作为对照观察。结果4个月饲养期间内无肠梗阻发。3段肠浆肌膜腔内脾组织再生良好,组织结构与大网膜内移植脾组织无明显差别,2段再生较差,1段形成脓肿。结论肠浆肌膜腔内移植脾组织的量较大,可作为自体脾组织的移植术式。