抑郁与卵巢癌风险增加相关。先前的研究表明，抑郁可导致全身性免疫抑制，可能改变抗肿瘤免疫反应。我们在三个研究中对卵巢肿瘤组织中收集的女性进行了抗肿瘤免疫反应特征的前诊断抑郁相关研究，包括T和B细胞和免疫球蛋白。这三个研究包括护士健康研究（NHS; n = 237）、NHSII（n = 137）和新英格兰病例对照研究（NECC; n = 215）。在诊断卵巢癌之前，报告抑郁症状高于临床相关分数、使用抗抑郁药物或医生诊断抑郁的女性被视为有前诊断抑郁。在肿瘤组织芯片上进行多重免疫荧光检测，以测量免疫细胞浸润。在汇总分析中，我们使用贝塔二项式模型估计了阴性与阳性肿瘤免疫细胞的比值比（OR）和95%置信区间（CI），比较了有与无抑郁的情况。我们采用Bonferroni校正来调整多重比较。在Bonferroni校正的p值为0.0045时，我们观察到抑郁状态与任何免疫标志物之间没有统计学显著的关联；然而，在名义p值为0.05时，有几个免疫标志物达到了显著水平。具体而言，患有抑郁的女性肿瘤中近期活化的细胞毒性（CD3+CD8+CD69+）和细胞精疲劳（CD3+Lag3+）T细胞的比值较没有抑郁的女性更高（OR = 1.36，95 %CI = 1.09-1.69和OR = 1.24，95 %CI = 1.01-1.53，分别）。当仅考虑高级别浆液性肿瘤时，这些关联结果基本相同（相似的OR分别为1.33和1.25）。患有抑郁的女性中，肿瘤浸润的浆细胞（CD138+）的比值减少（OR = 0.54，95 %CI = 0.33-0.90），对高级别浆液性肿瘤也相似，尽管没有统计学显著性。抑郁还与具有朴素和记忆B细胞（CD20+: OR = 0.54，95 %CI = 0.30-0.98）的比值减少和IgG（OR = 1.22，95 %CI = 0.97-1.53）的比值增加相关。我们的结果提供了暗示性证据，表明抑郁可能通过改变肿瘤免疫微环境，包括增加T细胞活化和衰竭，减少产生抗体的B细胞，影响卵巢癌的转归。需要进一步研究，使用临床抑郁指标和更大的样本来确认这些结果。版权所有 © 2023。Elsevier Inc.出版。

Depression is associated with a higher ovarian cancer risk. Prior work suggests that depression can lead to systemic immune suppression, which could potentially alter the anti-tumor immune response.We evaluated the association of pre-diagnosis depression with features of the anti-tumor immune response, including T and B cells and immunoglobulins, among women with ovarian tumor tissue collected in three studies, the Nurses' Health Study (NHS; n = 237), NHSII (n = 137) and New England Case-Control Study (NECC; n = 215). Women reporting depressive symptoms above a clinically relevant cut-point, antidepressant use, or physician diagnosis of depression at any time prior to diagnosis of ovarian cancer were considered to have pre-diagnosis depression. Multiplex immunofluorescence was performed on tumor tissue microarrays to measure immune cell infiltration. In pooled analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the positivity of tumor immune cells using a beta-binomial model comparing those with and without depression. We used Bonferroni corrections to adjust for multiple comparisons.We observed no statistically significant association between depression status and any immune markers at the Bonferroni corrected p-value of 0.0045; however, several immune markers were significant at a nominal p-value of 0.05. Specifically, there were increased odds of having recently activated cytotoxic (CD3+CD8+CD69+) and exhausted-like T cells (CD3+Lag3+) in tumors of women with vs. without depression (OR = 1.36, 95 %CI = 1.09-1.69 and OR = 1.24, 95 %CI = 1.01-1.53, respectively). Associations were comparable when considering high grade serous tumors only (comparable ORs = 1.33, 95 %CI = 1.05-1.69 and OR = 1.25, 95 %CI = 0.99-1.58, respectively). There were decreased odds of having tumor infiltrating plasma cells (CD138+) in women with vs. without depression (OR = 0.54, 95 %CI = 0.33-0.90), which was similar among high grade serous carcinomas, although not statistically significant. Depression was also related to decreased odds of having naïve and memory B cells (CD20+: OR = 0.54, 95 %CI = 0.30-0.98) and increased odds of IgG (OR = 1.22, 95 %CI = 0.97-1.53) in high grade serous carcinomas.Our results provide suggestive evidence that depression may influence ovarian cancer outcomes through changes in the tumor immune microenvironment, including increasing T cell activation and exhaustion and reducing antibody-producing B cells. Further studies with clinical measures of depression and larger samples are needed to confirm these results.Copyright © 2023. Published by Elsevier Inc.