Laboratoire Biostatistiques Epidémiologie Santé Publique, Team Cancer (EA 2415), and Oncodefi, Institut Universitaire de Recherche Clinique, Montpellier, France.
Institut Universitaire de Recherche Clinique, Biostatistics, Epidemiology and Public Health EA2415, Montpellier, France.
Front Immunol. 2018 Dec 19;9:3058. doi: 10.3389/fimmu.2018.03058. eCollection 2018.
The immune surveillance theory of cancer posits that the body's immune system detects and destroys randomly occurring malignant cells. This theory is based on the observation of the increased frequency of malignancies in primary and secondary immunodeficiencies, and is supported by the successful demonstration of immune augmentation in current oncological immune therapy approaches. We review this model in the context of Down syndrome (DS), a condition with a unique tumor profile and various immune defects. Children and adults with DS are more prone to infections due to anatomical reasons and a varying degree of T- and B-cell maturation defects, NK cell dysfunction, and chemotactic or phagocytic abnormalities. However, despite an increased incidence of lymphoblastic and myeloblastic leukemia of infants and children with DS, individuals with DS have a globally decreased incidence of solid tumors as compared to age-adjusted non-DS controls. Additionally, cancers that have been considered "proof of immune therapy principles," such as renal carcinoma, small cell lung carcinoma, and malignant melanoma, are less frequent in adults with DS compared to the general population. Thus, despite the combination of an increased risk of leukemia with detectable immune biological abnormalities and a clinical immunodeficiency, people with DS appear to be protected against many cancers. This observation does not support the immune surveillance theory in the context of DS and indicates a potential tumor-suppressive role for trisomy 21 in non-hematological malignancies.
癌症的免疫监视理论认为，人体的免疫系统会检测并破坏随机发生的恶性细胞。该理论基于原发性和继发性免疫缺陷中恶性肿瘤频率增加的观察结果，并得到当前肿瘤免疫治疗方法中免疫增强成功证明的支持。我们在唐氏综合征（DS）的背景下审查了该模型，唐氏综合征是一种具有独特肿瘤特征和各种免疫缺陷的疾病。由于解剖原因和 T 细胞和 B 细胞成熟缺陷、NK 细胞功能障碍以及趋化或吞噬异常的程度不同，唐氏综合征儿童和成人更容易感染。然而，尽管唐氏综合征婴儿和儿童的淋巴母细胞性和髓母细胞性白血病发病率增加，但与年龄调整后的非 DS 对照组相比，唐氏综合征个体的实体瘤总体发病率降低。此外，被认为“证明免疫治疗原则”的癌症，如肾细胞癌、小细胞肺癌和恶性黑色素瘤，在唐氏综合征成人中的发病率低于普通人群。因此，尽管白血病的风险增加与可检测的免疫生物学异常和临床免疫缺陷相结合，但唐氏综合征患者似乎免受许多癌症的侵害。这一观察结果并不支持 DS 背景下的免疫监视理论，并表明 21 三体在非血液恶性肿瘤中可能具有肿瘤抑制作用。
