Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy.
Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy.
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作者：
Barrett RL;Puré E
成纤维细胞在器官发生和组织结构和功能的完整性中起着重要作用。大多数实体瘤的生长依赖于由癌症相关成纤维细胞（CAF）和细胞外基质（ECM）组成的重塑“基质”，其在肿瘤发生、进展、转移和治疗抗性中起关键作用。最近的研究已经清楚地确定，基质的有效免疫抑制活性是基质可以促进肿瘤进展并赋予对基于免疫的疗法的抗性的主要机制。在此，我们回顾了最近的进展，确定基质依赖性机制，调节癌症相关的炎症和抗肿瘤免疫，特别是成纤维细胞和免疫细胞之间的相互作用。我们还审查了基质可以赋予抵抗实体瘤的免疫为基础的治疗和目前在基质靶向治疗的进展的潜在机制。
Fibroblasts play an essential role in organogenesis and the integrity of tissue architecture and function. Growth in most solid tumors is dependent upon remodeling ‘stroma’, composed of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), which plays a critical role in tumor initiation, progression, metastasis, and therapeutic resistance. Recent studies have clearly established that the potent immunosuppressive activity of stroma is a major mechanism by which stroma can promote tumor progression and confer resistance to immune-based therapies. Herein, we review recent advances in identifying the stroma-dependent mechanisms that regulate cancer-associated inflammation and antitumor immunity, in particular, the interactions between fibroblasts and immune cells. We also review the potential mechanisms by which stroma can confer resistance to immune-based therapies for solid tumors and current advancements in stroma-targeted therapies.