Exploiting regulatory T-cell populations for the immunotherapy of cancer.
Exploiting regulatory T-cell populations for the immunotherapy of cancer.
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利用调节性 T 细胞群进行癌症免疫治疗。
DOI：
10.1097/cji.0b013e31805ca058
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Exley,MarkA
中科院分区：
文献类型：
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作者：
vanderVliet,HansJJ;Koon,HenryB;Atkins,MichaelB;Balk,StevenP;Exley,MarkA
肿瘤逃离免疫系统阻碍了癌症的有效免疫治疗。最近的证据表明，在癌症患者中，两种先天性（“天然”）免疫调节 T 细胞群的活性改变可能会阻止有效抗肿瘤免疫反应的建立。这些是 CD4+ CD25+（天然）调节性 T 细胞和不变的自然杀伤 T 细胞，通常在协调对自身和非自身的免疫反应中发挥关键作用。对这些调节性 T 细胞群进行治疗性调节在临床上是可行的，并且与当前可用的免疫治疗策略相结合时，有可能诱导有效的抗肿瘤免疫反应。 背景一个多世纪以来，研究一直在寻找增强癌症患者免疫系统的方法，以根除逃避推定免疫监视后出现的肿瘤。随着对免疫系统的了解不断增加，打破肿瘤耐受性的免疫治疗策略从很大程度上非特异性（例如 Coley 毒素）演变为更特异性和越来越有效的癌症疫苗接种形式（参见参考文献 1、2）。然而，总体而言，治疗癌症的免疫治疗策略在临床上取得的成功有限，这显然是由于临床相关癌症患者的免疫缺陷以及多种肿瘤逃逸机制所致。肿瘤逃离免疫系统可归因于多种内在和外在因素，包括抗原加工和呈递途径成分的丢失、细胞死亡受体信号传导的改变、免疫抑制细胞因子的产生和T细胞反应抑制剂[例如白介素-10 (IL-10)、转化生长因子-β、半乳糖凝集素-1、精氨酸酶和吲哚胺2, 3-双加氧酶]以及免疫调节的改变T 细胞群（参见参考文献 3、4）。免疫调节 T 细胞群主要以 CD4+ CD25+（也称为“天然”）调节 T 细胞和不变自然杀伤 T 细胞 (iNKT) 为代表。 5 这些免疫调节细胞群的治疗性调节可能是成功诱导强效抗肿瘤免疫反应的关键因素。
Tumor escape from the immune system hampers effective immunotherapy for cancer. Recent evidence indicates that in cancer patients the altered activities of 2 innatelike (“natural”) immunoregulatory T-cell populations could prevent the establishment of effective antitumor immune responses. These are CD4+ CD25+(natural) regulatory T cells and invariant natural killer T cells, which normally play critical roles in orchestrating immune responses to self and nonself. Therapeutic modulation of these regulatory T-cell populations is clinically feasible and will potentially allow the induction of effective antitumor immune responses when combined with currently available immunotherapeutic strategies.BACKGROUNDFor over a century, research has sought ways to boost the immune system of cancer patients to eradicate tumors that arose after escaping presumptive immunosurveillance. With increasing knowledge of the immune system, immunotherapeutic strategies to break tolerance to the tumor evolved from largely nonspecific (eg, Coley's toxins) to more specific and increasingly potent forms of cancer vaccination (reviewed in Refs. 1, 2). Overall, however, immunotherapeutic strategies for the treatment of cancer have had limited clinical success apparently owing to immune defects of patients with clinically relevant cancer in combination with multiple tumor escape mechanisms. Tumor escape from the immune system can be attributed to several intrinsic and extrinsic factors, including loss of components of the antigen processing and presentation pathway, alterations in cell death receptor signaling, production of immunosuppressive cytokines, and inhibitors of T-cell responses [eg, interleukin-10 (IL-10), transforming growth factor-β, galectin-1, arginase, and indoleamine 2, 3-dioxygenase], and alterations in immunoregulatory T-cell populations (reviewed in Refs. 3, 4). Immunoregulatory T-cell populations are notably represented by CD4+ CD25+(also called “natural”) regulatory T cells and invariant natural killer T cells (iNKT). 5 Therapeutic modulation of these immunoregulatory cell populations could be a key factor involved in the successful induction of potent and effective antitumor immune responses.