Campisi Marco, Shelton Sarah E, Chen Minyue, Kamm Roger D, Barbie David A, Knelson Erik H
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cancers (Basel). 2022 Jul 22;14(15):3561. doi: 10.3390/cancers14153561.
Cell therapies, including adoptive immune cell therapies and genetically engineered chimeric antigen receptor (CAR) T or NK cells, have shown promise in treating hematologic malignancies. Yet, immune cell infiltration and expansion has proven challenging in solid tumors due to immune cell exclusion and exhaustion and the presence of vascular barriers. Testing next-generation immune therapies remains challenging in animals, motivating sophisticated ex vivo models of human tumor biology and prognostic assays to predict treatment response in real-time while comprehensively recapitulating the human tumor immune microenvironment (TIME). This review examines current strategies for testing cell-based cancer immunotherapies using ex vivo microphysiological systems and microfluidic technologies. Insights into the multicellular interactions of the TIME will identify novel therapeutic strategies to help patients whose tumors are refractory or resistant to current immunotherapies. Altogether, these microphysiological systems (MPS) have the capability to predict therapeutic vulnerabilities and biological barriers while studying immune cell infiltration and killing in a more physiologically relevant context, thereby providing important insights into fundamental biologic mechanisms to expand our understanding of and treatments for currently incurable malignancies.
细胞疗法，包括过继性免疫细胞疗法以及基因工程嵌合抗原受体（CAR）T细胞或NK细胞疗法，已在治疗血液系统恶性肿瘤方面展现出前景。然而，由于免疫细胞的排除和耗竭以及血管屏障的存在，免疫细胞浸润和扩增在实体瘤中已被证明具有挑战性。在动物中测试下一代免疫疗法仍然具有挑战性，这促使人们建立复杂的人类肿瘤生物学体外模型和预后分析方法，以便在全面重现人类肿瘤免疫微环境（TIME）的同时实时预测治疗反应。本综述探讨了使用体外微生理系统和微流控技术测试基于细胞的癌症免疫疗法的当前策略。对TIME多细胞相互作用的深入了解将有助于确定新的治疗策略，以帮助那些肿瘤对当前免疫疗法难治或耐药的患者。总之，这些微生理系统（MPS）有能力在更符合生理情况的背景下研究免疫细胞浸润和杀伤时预测治疗易损性和生物屏障，从而为基本生物学机制提供重要见解，以扩展我们对目前无法治愈的恶性肿瘤的理解和治疗方法。
