Johansson Anna, Hamzah Juliana, Ganss Ruth
Vascular Biology and Stromal Targeting, Harry Perkins Institute of Medical Research, The University of Western Australia, Centre for Medical Research, Nedlands, Western Australia 6009, Australia.
Targeted Drug Delivery, Imaging and Therapy, Harry Perkins Institute of Medical Research, The University of Western Australia, Centre for Medical Research, Nedlands, Western Australia 6009, Australia.
Biochim Biophys Acta. 2016 Jan;1865(1):3-13. doi: 10.1016/j.bbcan.2015.06.001. Epub 2015 Jun 10.
Current clinical success with anti-cancer immunotherapy provides exciting new treatment opportunities. While encouraging, more needs to be done to induce durable effects in a higher proportion of patients. Increasing anti-tumor effector T cell quantity or quality alone does not necessarily correlate with therapeutic outcome. Instead, the tumor microenvironment is a critical determinant of anti-cancer responsiveness to immunotherapy and can confer profound resistance. Yet, the tumor-promoting environment - due to its enormous plasticity - also delivers the best opportunities for adjuvant therapy aiming at recruiting, priming and sustaining anti-tumor cytotoxicity. While the tumor environment as an entity is increasingly well understood, current interventions are still broad and often systemic. In contrast, tumors grow in a highly compartmentalized environment which includes the vascular/perivascular niche, extracellular matrix components and in some tumors lymph node aggregates; all of these structures harbor and instruct subsets of immune cells. Targeting and re-programming specific compartments may provide better opportunities for adjuvant immunotherapy.
目前抗癌免疫疗法在临床上取得的成功带来了令人兴奋的新治疗机遇。尽管令人鼓舞，但仍需付出更多努力，以使更高比例的患者产生持久疗效。仅增加抗肿瘤效应T细胞的数量或质量并不一定与治疗结果相关。相反，肿瘤微环境是免疫疗法抗癌反应的关键决定因素，并且可能导致深度耐药。然而，促肿瘤环境——由于其巨大的可塑性——也为旨在募集、启动和维持抗肿瘤细胞毒性的辅助治疗提供了最佳机会。虽然肿瘤环境作为一个整体越来越为人所熟知，但目前的干预措施仍然宽泛且往往是全身性的。相比之下，肿瘤生长在一个高度分隔的环境中，其中包括血管/血管周围微环境、细胞外基质成分，在某些肿瘤中还包括淋巴结聚集物；所有这些结构都容纳并指导免疫细胞亚群。靶向和重新编程特定的分隔区域可能为辅助免疫治疗提供更好的机会。
