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The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian cancer and the impact of NEOADJUVANT chemotherapy.
Virchows Archiv ( IF 3.5 ) Pub Date : 2020-03-16 , DOI: 10.1007/s00428-020-02795-8
J O A M van Baal 1 , C A R Lok 1 , E S Jordanova 1 , H Horlings 2 , W J van Driel 1 , F C Amant 1 , K K Van de Vijver 2, 3
Affiliation  

Peritoneal metastases of high-grade serous ovarian cancer (HGSOC) are small-sized deposits with superficial growth toward the peritoneal cavity. It is unknown whether integrity of the peritoneal elastic lamina (PEL) correlates with the peritoneal tumor microenvironment (pTME) and whether neoadjuvant chemotherapy (NACT) affects the pTME. We explored integrity of PEL, composition of pTME, effects of NACT, and the prognostic implications in patients with extensive peritoneal metastases of HGSOC. Peritoneal samples (n = 69) were collected during cytoreductive surgery between 2003 and 2016. Clinical data were collected from medical charts. Integrity of PEL was evaluated with elastic stains. T cell (CD3, CD8) and M2-macrophage markers (CD163) were scored using algorithms created in definiens tissue studio. Patients with a disrupted PEL (n = 39; 57%), more often had residual disease after surgery (p = 0.050), compared to intact PEL. An intact PEL was associated with increased intraepithelial (ie) CD8+ cells (p = 0.032), but was not correlated with improved survival. After NACT, increased ieCD3+ cells were shown, compared to no-NACT (p = 0.044). Abundance of total CD3+ and CD8+ cells were associated with PFS (multivariate HR 0.40; 95%CI 0.23–0.69 and HR 0.49; 95%CI 0.29–0.83) and OS (HR 0.33; 95%CI 0.18–0.62 and HR 0.36; 95%CI 0.20–0.64). M2-macrophage infiltration was not correlated with survival. NACT increases abundance of ieCD3+ cells in peritoneal metastases of HGSOC. Increase of CD3+ and CD8+ cells is associated with improved PFS and OS. This suggests that CD3+ and CD8+ cells may function as prognostic biomarkers. Their role as predictive biomarker for chemotherapy or immunotherapy response in HGSOC warrants further research.



中文翻译:

腹膜肿瘤微环境对高级别浆液性卵巢癌腹膜转移侵袭的影响以及NEOADJUVANT化疗的影响。

高度浆液性卵巢癌(HGSOC)的腹膜转移是小沉积物,向腹膜腔表面生长。尚不清楚腹膜弹性层(PEL)的完整性是否与腹膜肿瘤微环境(pTME)相关,以及新辅助化疗(NACT)是否会影响pTME。我们探索了PEL的完整性,pTME的组成,NACT的作用以及HGSOC广泛腹膜转移患者的预后意义。腹膜样品(n = 69)是在2003年至2016年间进行的细胞减灭术中收集的。临床数据来自医学图表。用弹性污点评价PEL的完整性。使用在definiens组织工作室中创建的算法对T细胞(CD3,CD8)和M2-巨噬细胞标记(CD163)进行评分。与 完整的PEL相比,PEL受损的患者(n  = 39; 57%)在手术后残留疾病的发生率更高(p = 0.050)。完整的PEL与上皮内(即)CD8 +细胞增加有关(p  = 0.032),但与存活率提高无关。NACT后,与无NACT相比,显示出增加的ieCD3 +细胞(p = 0.044)。总的CD3 +和CD8 +细胞的丰度与PFS(多元HR 0.40; 95%CI 0.23-0.69和HR 0.49; 95%CI 0.29-0.83)和OS(HR 0.33; 95%CI 0.18-0.62和HR 0.36; 95)相关%CI 0.20–0.64)。M2巨噬细胞浸润与生存率无关。NACT增加HGSOC腹膜转移中ieCD3 +细胞的丰度。CD3 +和CD8 +细胞的增加与PFS和OS的改善有关。这表明CD3 +和CD8 +细胞可能充当预后生物标志物。它们作为HGSOC中化学疗法或免疫疗法反应的预测性生物标志物的作用值得进一步研究。

更新日期:2020-03-16
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