Background: Evidence is accumulating that immune cells play a prominent role in pancreatic cancer etiology but prospective investigations are missing. Methods: We conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sublineages: total CD3+, CD8+, CD4+, and FOXP3+ regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. ORs with 95% confidence intervals were estimated using logistic regressions, modeling relative counts of immune cells on a continuous scale. Results: Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in subgroup analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8+ were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up. Conclusions: These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8+ cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease. Impact: We have shown, for the first time, that increased relative counts of regulatory T cells and lower relative counts of CD8+, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development. See related commentary by Michaud and Kelsey, [p. 2176][1] This article is featured in Highlights of This Issue, [p. 2141][2] [1]: /lookup/volpage/30/2176?iss=12 [2]: /lookup/volpage/30/2141?iss=12

中文翻译：

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循环免疫细胞是胰腺癌风险的决定因素吗？使用表观遗传细胞计数测量的前瞻性研究

背景：越来越多的证据表明免疫细胞在胰腺癌病因学中起重要作用，但缺乏前瞻性研究。方法：我们在欧洲癌症与营养前瞻性调查 (EPIC) 研究中对 502 对新发胰腺癌病例和匹配的对照组进行了嵌套病例对照研究。通过 qRT-PCR 测量循环免疫细胞（中性粒细胞和淋巴细胞亚系：总 CD3+、CD8+、CD4+ 和 FOXP3+ 调节性 T 细胞 (Tregs) 相对于有核细胞（白细胞）的相对计数。具有 95% 置信区间的 ORs使用逻辑回归进行估计，在连续尺度上模拟免疫细胞的相对计数结果：免疫细胞类型的相对计数均不单独进行，也没有相互调整与胰腺癌风险相关。然而，在按滞后时间分层的亚组分析中，较高的 Treg 相对计数和较低的 CD8+ 相对计数与在随访的前 5 年内诊断出的参与者的胰腺癌风险增加显着相关。结论：这些结果可能反映了反向因果关系，因为在更接近发展为临床表现疾病的晚期潜伏胰腺癌个体中，Tregs 的相对计数较高而 CD8+ 细胞的计数较低。影响：我们首次表明，调节性 T 细胞的相对数量增加和 CD8+、细胞毒性 T 细胞的相对数量减少可能与胰腺癌风险或相对晚期肿瘤发展有关。见 Michaud 和 Kelsey 的相关评论，[p. 2176][1] 这篇文章被收录在本期的亮点中，[p. 2141][2] [1]:/lookup/volpage/30/2176?iss=12 [2]:/lookup/volpage/30/2141?iss=12