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Immunotyping in tubo‐ovarian high‐grade serous carcinoma by PD‐L1 and CD8+ T‐lymphocytes predicts disease‐free survival
APMIS ( IF 2.2 ) Pub Date : 2021-01-17 , DOI: 10.1111/apm.13116
Akriti Bansal 1 , Radhika Srinivasan 2 , Manish Rohilla 2 , Bhavana Rai 3 , Arvind Rajwanshi 2 , Vanita Suri 4 , Subhas Chandra Saha 4
Affiliation  

PD‐L1 immune checkpoint inhibitor expression was evaluated in high‐grade serous carcinoma (HGSC) ovary in the context of the overall immune landscape to determine its prognostic value. Consecutive cases of HGSC, 50 who underwent upfront surgery followed by adjuvant chemotherapy (HGSC‐U) and 50 who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (HGSC‐PC) were selected. In HGSC‐PC cases, the pre‐NACT ascitic fluid cell blocks were included. Tumor‐infiltrating lymphocytes (TILs) were scored, hotspots chosen for tissue microarray construction and immunohistochemistry performed and scored for CD4 and CD8 lymphocyte subsets, CD68+ tumor‐associated macrophages (TAMs), PD‐1 and PD‐L1 expression. HGSC‐post‐chemotherapy showed increased TILs, predominantly CD8+T‐lymphocytes, compared to HGSC‐U. HGSC showed PD‐L1 expression on tumor cells and/or TAMs in 60% cases with a linear correlation to CD4+, CD8+ TIL levels. Concordant PD‐L1 expression was seen in matched pre‐ and post‐NACT tumor cells. HGSC‐PC showed higher expression of PD‐L1. There was no association of PD‐L1 cumulative proportion score or tumor cell score with outcome. Taking a cutoff for PD‐L1 CPS at 10%, immunotype I (PD‐L1+/CD‐8+), corresponding to tumors with adaptive immune evasion, showed worst disease‐free survival compared to all other immunotypes (p = 0.03) and was more significant (p = 0.01) when compared to immunotype III (PD‐L1+/CD8−). Immunotyping based on PD‐L1/CD8+ expression correlates to prognosis and outcome.

中文翻译:

PD-L1和CD8 + T淋巴细胞在大卵巢卵巢浆液性癌中的免疫分型可预测无病生存

在整体免疫环境中评估了PD-L1免疫检查点抑制剂在高度浆液性癌(HGSC)卵巢中的表达,以确定其预后价值。选择连续发生HGSC的病例,其中50例行了前期手术,然后进行了辅助化疗(HGSC-U),另外50例进行了新辅助化疗(NACT),之后进行了间歇性减脂术(HGSC-PC)。在HGSC-PC病例中,包括了NACT之前的腹水细胞块。对肿瘤浸润淋巴细胞(TIL)进行评分,选择热点进行组织微阵列构建和免疫组织化学分析,并对CD4和CD8淋巴细胞亚群,CD68 +肿瘤相关巨噬细胞(TAM),PD-1和PD-1L1表达进行评分。与HGSC-U相比,HGSC化学疗法后的TIL增加,主要是CD8 + T淋巴细胞。HGSC在60%的病例中显示PD-L1在肿瘤细胞和/或TAM上的表达与CD4 +,CD8 + TIL水平呈线性相关。在匹配的NACT之前和之后的肿瘤细胞中观察到一致的PD-L1表达。HGSC-PC显示PD-L1的更高表达。PD-L1累积比例评分或肿瘤细胞评分与结局无关联。与10%的PD-L1 CPS截断值相比,免疫I型(PD-L1 + / CD-8 +)对应于具有适应性免疫逃避的肿瘤,与所有其他免疫类型相比,无病生存期最差(p  = 0.03), 与免疫III型(PD-L1 + / CD8-)相比,具有更显着的意义(p = 0.01)。基于PD‐L1 / CD8 +表达的免疫分型与预后和结果相关。
更新日期:2021-01-17
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