Koo Jane, Hayashi Masanori, Verneris Michael R, Lee-Sherick Alisa B
Department of Pediatric Hematology/Oncology/Bone Marrow Transplant, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, United States.
Front Oncol. 2020 Dec 14;10:581107. doi: 10.3389/fonc.2020.581107. eCollection 2020.
For many pediatric sarcoma patients, multi-modal therapy including chemotherapy, radiation, and surgery is sufficient to cure their disease. However, event-free and overall survival rates for patients with more advanced disease are grim, necessitating the development of novel therapeutic approaches. Within many pediatric sarcomas, the normal immune response, including recognition and destruction of cancer cells, is lost due to the highly immune suppressive tumor microenvironment (TME). In this setting, tumor cells evade immune detection and capitalize on the immune suppressed microenvironment, leading to unchecked proliferation and metastasis. Recent preclinical and clinical approaches are aimed at understanding this immune suppressive microenvironment and employing cancer immunotherapy in an attempt to overcome this, by renewing the ability of the immune system to recognize and destroy cancer cells. While there are several factors that drive the attenuation of immune responses in the sarcoma TME, one of the most remarkable are tumor associated macrophage (TAMs). TAMs suppress immune cytolytic function, promote tumor growth and metastases, and are generally associated with a poor prognosis in most pediatric sarcoma subtypes. In this review, we summarize the mechanisms underlying TAM-facilitated immune evasion and tumorigenesis and discuss the potential therapeutic application of TAM-focused drugs in the treatment of pediatric sarcomas.
对于许多小儿肉瘤患者而言,包括化疗、放疗和手术在内的多模式疗法足以治愈他们的疾病。然而,病情更严重的患者的无事件生存率和总生存率不容乐观,因此需要开发新的治疗方法。在许多小儿肉瘤中,由于高度免疫抑制的肿瘤微环境(TME),包括对癌细胞的识别和破坏在内的正常免疫反应丧失。在这种情况下,肿瘤细胞逃避免疫检测并利用免疫抑制的微环境,导致不受控制的增殖和转移。最近的临床前和临床方法旨在了解这种免疫抑制微环境,并通过恢复免疫系统识别和破坏癌细胞的能力来采用癌症免疫疗法,以试图克服这一问题。虽然有几个因素导致肉瘤TME中免疫反应减弱,但最显著的因素之一是肿瘤相关巨噬细胞(TAM)。TAM抑制免疫细胞溶解功能,促进肿瘤生长和转移,并且在大多数小儿肉瘤亚型中通常与预后不良相关。在这篇综述中,我们总结了TAM促进免疫逃逸和肿瘤发生的潜在机制,并讨论了以TAM为靶点的药物在小儿肉瘤治疗中的潜在治疗应用。