Lutgendorf Susan K, Lamkin Donald M, DeGeest Koen, Anderson Barrie, Dao Minh, McGinn Stephanie, Zimmerman Bridget, Maiseri Heena, Sood Anil K, Lubaroff David M
Department of Psychology, E11 Seashore Hall, University of Iowa, Iowa City, IA 52242, USA.
Brain Behav Immun. 2008 Aug;22(6):890-900. doi: 10.1016/j.bbi.2007.12.012. Epub 2008 Feb 13.
The adaptive immune response of ovarian cancer patients has been linked to survival, and is known to be impaired in the tumor microenvironment. Little is known about relationships between biobehavioral factors such as depressed mood and anxiety and the adaptive immune response in ovarian cancer. Thirty-seven patients with epithelial ovarian cancer and 14 patients with benign ovarian neoplasms completed psychosocial questionnaires pre-surgery. Lymphocytes from peripheral blood, tumor, and ascites (fluid around the tumor), were obtained on the day of surgery. Expression of the Type-1 cytokine interferon-gamma (IFN gamma), and the Type-2 cytokine interleukin-4 (IL-4) by T-helper (CD4(+)) and T-cytotoxic (CD8(+)) cells was measured under autologous tumor-stimulated, polyclonally-stimulated, or unstimulated conditions. Links with mood were examined. Among cancer patients, marked elevations in unstimulated and tumor-stimulated Type-2 responses were seen, particularly in ascites and tumor-infiltrating lymphocytes (P values<0.01). With polyclonal stimulation, lymphocytes from all compartments expressed elevated Type-1 cytokines (P values<0.014). Depressed and anxious mood were both associated with significantly lower ratios of polyclonally-stimulated CD4(+) cells producing IFN gamma (TH(1) cells) vs. IL-4 (TH(2) cells) in all compartments (depressed mood: P=0.012; anxiety: P=0.038) and depressed mood was also related to lower ratios of polyclonally-stimulated CD8(+) cells producing IFN gamma (TC(1)) vs. IL-4 (TC(2)) (P=0.035). Although effects of polyclonal stimulation should be generalized with caution to the in vivo immune response, findings suggest that depressed and anxious mood are associated with greater impairment of adaptive immunity in peripheral blood and in the tumor microenvironment among ovarian cancer patients.
卵巢癌患者的适应性免疫反应与生存率相关,且已知在肿瘤微环境中会受到损害。对于诸如情绪低落和焦虑等生物行为因素与卵巢癌适应性免疫反应之间的关系,人们了解甚少。37例上皮性卵巢癌患者和14例卵巢良性肿瘤患者在手术前完成了心理社会问卷调查。在手术当天采集外周血、肿瘤及腹水(肿瘤周围的液体)中的淋巴细胞。在自体肿瘤刺激、多克隆刺激或未刺激条件下,测量辅助性T细胞(CD4(+))和细胞毒性T细胞(CD8(+))产生的1型细胞因子干扰素-γ(IFNγ)和2型细胞因子白细胞介素-4(IL-4)的表达。研究了其与情绪的关联。在癌症患者中,未刺激和肿瘤刺激下的2型反应显著升高,尤其是在腹水和肿瘤浸润淋巴细胞中(P值<0.01)。在多克隆刺激下,所有区室的淋巴细胞均表达升高的1型细胞因子(P值<0.014)。情绪低落和焦虑均与所有区室中多克隆刺激产生IFNγ的CD4(+)细胞(TH(1)细胞)与产生IL-4的CD4(+)细胞(TH(2)细胞)的比例显著降低相关(情绪低落:P = 0.012;焦虑:P = 0.038),情绪低落还与多克隆刺激产生IFNγ的CD8(+)细胞(TC(1))与产生IL-4的CD8(+)细胞(TC(2))的比例降低有关(P = 0.035)。尽管多克隆刺激的效应在推广至体内免疫反应时应谨慎,但研究结果表明,情绪低落和焦虑与卵巢癌患者外周血和肿瘤微环境中适应性免疫的更大损害相关。