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非裔美国女性高级别浆液性卵巢癌中可靶向的免疫调节分子表达:来自非裔美国癌症流行病学研究(AACES)的112例病例的PD-L1和IDO研究

Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women: A Study of PD-L1 and IDO in 112 Cases From the African American Cancer Epidemiology Study (AACES).

作者信息

Mills Anne M, Peres Lauren C, Meiss Alice, Ring Kari L, Modesitt Susan C, Abbott Sarah E, Alberg Anthony J, Bandera Elisa V, Barnholtz-Sloan Jill, Bondy Melissa L, Cote Michele L, Funkhouser Ellen, Moorman Patricia G, Peters Edward S, Schwartz Ann G, Terry Paul D, Wallace Kristin, Schildkraut Joellen M

机构信息

Departments of Pathology (A.M.M., A.M.) Public Health Sciences (L.C.P., S.E.A., J.M.S.) Obstetrics and Gynecology (K.L.R., S.C.M.), University of Virginia, Charlottesville, Virginia Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia (A.J.A.) Department of Public Health Sciences, Medical University of South Carolina, Charleston (K.W.), South Carolina Department of Population Science, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (E.V.B.) Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio (J.B.-S.) Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, Texas (M.L.B.) Department of Oncology and the Karmanos Cancer Institute Population Studies and Disparities Research Program, Wayne State University, Detroit, Michigan (M.L.C, A.G.S.) Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama (E.F.) Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina (P.G.M.) Epidemiology Program, Louisiana State University Health Sciences Center School of Public Health, New Orleans, Louisiana (E.S.P.) Department of Medicine, University of Tennessee Medical Center-Knoxville, Knoxville, Tennessee (P.D.T.).

出版信息

Int J Gynecol Pathol. 2019 Mar;38(2):157-170. doi: 10.1097/PGP.0000000000000494.

Abstract

African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed <10% staining, and no cases exceeded 25% positivity. The majority of PD-L1-positive cases coexpressed IDO. PD-L1 and IDO expression was associated with higher CD8 and FOX3p counts (P<0.05). No association was observed between PD-L1 and IDO and survival. In summary, expression of PD-L1 and IDO is seen in a subset of high-grade serous ovarian carcinoma from African American women and is correlated with elevated lymphocyte infiltration. While PD-L1 and IDO co-expression suggests a role for dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.

摘要

与欧洲裔女性相比,患有高级别浆液性卵巢癌的非裔美国女性预后更差。尽管这种差异部分归因于获得医疗服务的差异,但肿瘤免疫微环境也可能起作用。诸如程序性细胞死亡配体-1(PD-L1)和吲哚胺2,3-双加氧酶(IDO)等可靶向免疫调节分子的表达尤其令人关注,因为它可能有助于指导该人群的治疗。利用非裔美国女性卵巢癌最大规模研究——非裔美国癌症流行病学研究中的病例,我们对112例高级别浆液性卵巢癌中的PD-L1和IDO表达进行了特征分析。进行了PD-L1、IDO、CD8、FOX3p和CD68的免疫组织化学检测。PD-L1和IDO按阳性肿瘤细胞和肿瘤相关免疫细胞的百分比进行评分。CD8和FOX3p计数在10个高倍视野中进行平均。采用Cox比例风险回归评估PD-L1和IDO表达与生存之间的关联。分别有29%和58%的病例肿瘤细胞PD-L1和IDO呈阳性。大多数病例染色<10%,无病例超过25%阳性。大多数PD-L1阳性病例同时表达IDO。PD-L1和IDO表达与较高的CD8和FOX3p计数相关(P<0.05)。未观察到PD-L1和IDO与生存之间的关联。总之,在非裔美国女性的一部分高级别浆液性卵巢癌中可见PD-L1和IDO表达,且与淋巴细胞浸润增加相关。虽然PD-L1和IDO共表达提示双重免疫治疗可能起作用,但PD-L1和IDO的弥漫性表达罕见,这就需要谨慎看待免疫治疗反应的可能性。

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