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

1. Download : Download high-res image (268KB)
2. Download : Download full-size image

     

Immunotherapy in Hodgkin and non-Hodgkin lymphoma: Innate,adaptive and targeted immunological strategies

Since the clinical introduction of anti-CD20 monoclonal antibodies into lymphoma treatment, immunologic approaches in lymphoma have made substantial progress. Advances in our understanding of tumor immunology have led to the development of strategies to overcome immunologic barriers responsible for an ineffective immune response. Specifically, therapeutic agents have been developed and tested against molecules that are responsible for T-cell exhaustion. The use of monoclonal antibodies against immune checkpoints in the adaptive immune system, such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, has changed the landscape of cancer therapy including the treatment of lymphoma. This achievement has recently been accompanied by the development of novel immune checkpoint inhibitors targeting the innate immune system, including the CD47-SIRPα signaling pathway, and this approach has yielded promising results. To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells.     

骨免疫学对骨质疏松症的调控作用研究进展

骨质疏松症是慢性全身性骨病，主要表现为骨量丢失、骨微结构退化，最终导致骨骼的脆性升高，骨折风险增高。目前中国老龄化人数逐步增加，已经步入老龄社会，骨质疏松及其导致的脆性骨折发病率逐年上升，极大地影响了患者的生命安全和生活质量，已经成为亟待解决的难题。在骨免疫学这一概念出现之前，由于免疫细胞在骨髓中形成，所以皆认为骨骼对免疫系统至关重要。但是免疫系统对骨骼的调控功能尚不是很清楚。2000年，Arron在Nature杂志上提出“骨免疫学”这一概念，并指出骨骼与免疫系统之间存在复杂的相互调控作用。自此之后，骨免疫学逐渐成为代谢性骨关节疾病的研究热点。骨免疫学在骨重建过程中具有重要的调控作用，其主要研究内容是阐明免疫系统、骨骼，两者之间存在密切复杂的互相调控机制。骨质疏松症的发生发展过程中，OPG/RANK/RANKL信号系统、免疫细胞及其产生的细胞因子都具有决定性的作用。骨免疫学为抗骨质疏松新型药物的研发奠定了理论根基。