Texas Children's Cancer Center, Center for Cell & Gene Therapy, Departments of Pediatrics and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Clin Immunol. 2011 Aug;140(2):119-29. doi: 10.1016/j.clim.2010.10.005. Epub 2010 Nov 20.
Vα24-invariant natural killer T cells (NKTs) are strictly CD1d-restricted, and CD1d expression has been found in several types of leukemia and lymphoma as well as in brain tumors suggesting that these malignancies could be targeted for direct NKT-cell cytotoxicity. Several studies have revealed strong positive associations between the numbers of tumor-infiltrating or circulating NKTs with improved disease outcome in patients with diverse types of CD1d-negative solid tumors. The mechanism by which NKTs mediate anti-tumor activity against CD1d-negative tumors has long remained enigmatic. Recent evidence indicates that NKTs can suppress tumor growth indirectly by targeting CD1d-positive elements of tumor-supportive stroma such as tumor-associated macrophages. This review summarizes the current knowledge about the mechanisms that regulate NKT-cell localization to the tumor site and their interaction with the tumor microenvironment. The discussed strategies for pharmacologic modulation and genetic engineering of NKTs may lead to development of effective and broadly applicable immunotherapies of cancer.
不变自然杀伤 T 细胞 (NKT) 是严格依赖于 CD1d 的，几种类型的白血病和淋巴瘤以及脑肿瘤中都发现了 CD1d 的表达，这表明这些恶性肿瘤可能成为直接 NKT 细胞细胞毒性作用的靶点。几项研究表明，肿瘤浸润或循环 NKT 细胞数量与不同类型 CD1d 阴性实体瘤患者的改善疾病结局之间存在强烈的正相关关系。NKT 细胞介导对 CD1d 阴性肿瘤的抗肿瘤活性的机制长期以来一直是个谜。最近的证据表明，NKT 细胞可以通过靶向肿瘤支持基质中 CD1d 阳性成分（如肿瘤相关巨噬细胞）来间接抑制肿瘤生长。这篇综述总结了目前关于调节 NKT 细胞定位到肿瘤部位及其与肿瘤微环境相互作用的机制的知识。讨论的 NKT 细胞的药理学调节和基因工程策略可能会导致开发有效的、广泛适用的癌症免疫疗法。
