Nowicki Marek J, Vigen Cheryl, Mack Wendy J, Seaberg Eric, Landay Alan, Anastos Kathryn, Young Mary, Minkoff Howard, Greenblatt Ruth, Levine Alexandra M
Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
AIDS Res Hum Retroviruses. 2008 Feb;24(2):163-8. doi: 10.1089/aid.2007.0119.
Evidence indicates that immunosupression is associated with the development of certain cancers. The pathogenesis of HIV disease includes an alteration in innate immunity, mediated through NK and NKT cells. The evaluation of innate immune status in HIV patients prior to cancer diagnosis may identify the specific immunological events preceding the development of malignant disease. We evaluated the association between immunophenotypically defined NK, NKT, and CD8(+) cell percentages and incident malignancies in 1817 HIV(+) women in the Women's Interagency HIV Study (WIHS) who were followed for a median of 7.5 years. A total of 52 incident cancers of 20 different sites were identified. Compared to cancer-free women, cancer cases were older (p < 0.01), more likely to be anti-HCV(+) (p = 0.02), and had higher baseline median HIV RNA levels than controls. The CD8(+), NK, and NKT percents at baseline were not related to cancer risk. However, when time-dependent values for NKT cells were used, higher levels of NKT cells were associated with a reduced risk of cancer (adjusted hazard ratio = 0.67, 95% CI = 0.50, 0.89 per NKT percentage point). In addition to the loss of CD4(+) lymphocytes and an increased risk of opportunistic infections, HCV coinfected individuals may also experience alterations in innate immunity, including reduced NKT and NK cell number and possibly their function. In time-dependent analyses, increased numbers of NKT cells were associated with a reduced risk of cancer. HIV-induced innate immune dysfunction may contribute to the eventual emergence of cancer in the setting of existing coinfections and altered immunosurveillance.
有证据表明免疫抑制与某些癌症的发生有关。HIV疾病的发病机制包括通过自然杀伤（NK）细胞和自然杀伤T（NKT）细胞介导的固有免疫改变。在癌症诊断之前评估HIV患者的固有免疫状态，可能会识别出恶性疾病发生之前的特定免疫事件。我们在女性机构间HIV研究（WIHS）中评估了1817名HIV阳性女性的免疫表型定义的NK、NKT和CD8(+)细胞百分比与新发恶性肿瘤之间的关联，这些女性的中位随访时间为7.5年。共识别出20个不同部位的52例新发癌症。与未患癌症的女性相比，癌症患者年龄更大（p < 0.01），更可能抗丙型肝炎病毒（HCV）阳性（p = 0.02），且基线时HIV RNA水平中位数高于对照组。基线时的CD8(+)、NK和NKT百分比与癌症风险无关。然而，当使用NKT细胞的时间依赖性值时，较高水平的NKT细胞与较低的癌症风险相关（调整后的风险比 = 0.67，95%置信区间 = 0.50，0.89，每NKT百分比点）。除了CD4(+)淋巴细胞减少和机会性感染风险增加外，合并HCV感染的个体也可能经历固有免疫改变，包括NKT和NK细胞数量减少以及可能的功能改变。在时间依赖性分析中，NKT细胞数量增加与较低的癌症风险相关。HIV诱导的固有免疫功能障碍可能在存在合并感染和免疫监视改变的情况下促成癌症的最终发生。
