Unraveling the Tumor Microenvironment and PD-L1 Expression across Tissue Types in High-Grade Serous Ovarian Cancer in the NeoPembrOV/GINECO Phase II Randomized Trial.

experimental_design

PD-L1 expression was assessed for 85 patients (56 on metastasis and 29 on tubo-ovary) using tumor proportion score (TPS) and immune cell (IC) score, considering positivity if ≥1% and high expression if ≥5%.

对85名患者（56名转移患者和29名输卵管卵巢患者）进行了PD-L1表达的评估，使用肿瘤比例评分（TPS）和免疫细胞（IC）评分，如果≥1%则认为是阳性，如果≥5%则认为是高表达。

RNA sequencing and multiplex immunofluorescence were conducted.

进行了RNA测序和多重免疫荧光技术。

The Australian Ovarian Cancer Study was used as an external validation cohort.

澳大利亚卵巢癌研究被用作外部验证队列。

Results

PD-L1 was primarily expressed by tumor cells in tubo-ovaries and by ICs in metastases.

PD-L1主要由输卵管卵巢肿瘤细胞表达，而在转移部位则主要由浸润细胞表达。

The IC score assessed on the metastases was associated with a longer progression-free survivalin the pembrolizumab arm compared with the control arm.

在转移部位评估的浸润细胞评分与pembrolizumab组相比，与对照组相比，与更长的无进展生存期相关。

Compared with tubo-ovaries, metastases were enriched in T and B cells as well as in granzyme B (GZMB) CD8 cytotoxic T-cell signatures.

与输卵管卵巢相比，转移性病变在T细胞和B细胞以及颗粒酶B（GZMB）CD8细胞毒性T细胞特征中富集。

In metastases, the IC score was associated with immune infiltration and overexpression of additional immune checkpoints, such as IDO1, LAG3, and ICOS, whereas TPS was associated with cell proliferation, immune infiltration, and IFN-γ pathways.

在转移性病变中，免疫检查点（IC）评分与免疫浸润和额外免疫检查点（如IDO1、LAG3和ICOS）的过度表达有关，而肿瘤突变负荷（TPS）与细胞增殖、免疫浸润和IFN-γ通路有关。

In tubo-ovaries, TPS was associated with pathways linked to cell proliferation and antigen presentation but was depleted in activated immune pathways, and CD274 expression was correlated with hypoxia and PI3K/Akt/mTOR signaling.

在输卵管卵巢中，TPS 与细胞增殖和抗原呈递相关通路有关，但在激活的免疫通路中减少，而 CD274 表达与缺氧和 PI3K/Akt/mTOR 信号通路相关。

Conclusions

Distinct PD-L1 expression patterns across tissue types are associated with different biological pathways and tumor microenvironments in ovarian cancer, affecting PD-L1 predictive value.

不同组织类型中 PD-L1 表达模式的差异与卵巢癌中的不同生物通路和肿瘤微环境相关，影响 PD-L1 的预测价值。

Our results provide novel insights into high-grade serous ovarian cancer biology for tailoring immunotherapy in patients with ovarian cancer.

我们的研究结果为高级别浆液性卵巢癌的生物学提供了新的见解，有助于为卵巢癌患者定制免疫治疗方案。