Aldinucci Donatella, Celegato Marta, Casagrande Naike
Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, Italy.
Department of Experimental Oncology 2, CRO Aviano National Cancer Institute, Aviano, Italy.
Cancer Lett. 2016 Sep 28;380(1):243-52. doi: 10.1016/j.canlet.2015.10.007. Epub 2015 Oct 23.
Classical Hodgkin lymphoma (cHL) is characterized by few tumor cells surrounded by immune cells, fibroblasts, specialized mesenchymal stromal cells and endothelial cells, representing together with their products an active part of the disease. Hodgkin and Reed-Sternberg (HRS) cells can secrete cytokines/chemokines and angiogenic factors capable of recruiting and/or inducing the proliferation of the surrounding cells and can also interact with distant sites of the microenvironment by secreting exosomes. To escape from a useful anti-tumor response due to the recognition by T and NK cells, HRS cells down-regulate HLA molecules, produce immune suppressive cytokines that inhibit cytotoxic responses, and induce an immunosuppressive phenotype on T lymphocytes and Monocytes. HRS cells survive, proliferate and are protected from the cytotoxic effects of chemotherapy agents by soluble factors or by the direct contact with inflammatory and stromal cells of the tumor microenvironment (TME). A summary of the current knowledge about classical Hodgkin Lymphoma focusing on the cross-talk between tumor cells and the microenvironment leading to immune-escape, angiogenesis tumor growth/survival and drug resistance will be reviewed here.
经典型霍奇金淋巴瘤（cHL）的特征是少数肿瘤细胞被免疫细胞、成纤维细胞、特殊间充质基质细胞和内皮细胞所包围，这些细胞及其产物共同构成了疾病的活跃部分。霍奇金和里德-斯腾伯格（HRS）细胞可分泌细胞因子/趋化因子和血管生成因子，能够招募和/或诱导周围细胞增殖，还可通过分泌外泌体与远处的微环境部位相互作用。为逃避因T细胞和NK细胞识别而产生的有效抗肿瘤反应，HRS细胞下调HLA分子，产生抑制细胞毒性反应的免疫抑制细胞因子，并在T淋巴细胞和单核细胞上诱导免疫抑制表型。HRS细胞通过可溶性因子或与肿瘤微环境（TME）的炎症和基质细胞直接接触而存活、增殖并免受化疗药物的细胞毒性作用。本文将综述目前关于经典型霍奇金淋巴瘤的知识总结，重点关注肿瘤细胞与微环境之间导致免疫逃逸、血管生成、肿瘤生长/存活和耐药性的相互作用。
