Background

In colorectal and breast cancer, the density and localisation of immune infiltrates provides strong prognostic information. We asked whether similar automated quantitation and combined analysis of immune infiltrates could refine prognostic information in high-grade serous ovarian carcinoma (HGSOC) and tested associations between patterns of immune response and genomic driver alterations.

Methods

Epithelium and stroma were semi-automatically segmented and the infiltration of CD45RO⁺, CD8⁺ and CD68⁺ cells was automatically quantified from images of 332 HGSOC patient tissue microarray cores.

Results

Epithelial CD8 [p = 0.027, hazard ratio (HR) = 0.83], stromal CD68 (p = 3 × 10⁻⁴, HR = 0.44) and stromal CD45RO (p = 7 × 10⁻⁴, HR = 0.76) were positively associated with survival and remained so when averaged across the tumour and stromal compartments. Using principal component analysis, we identified optimised multiparameter survival models combining information from all immune markers (p = 0.016, HR = 0.88). There was no significant association between PTEN expression, type of TP53 mutation or presence of BRCA1/BRCA2 mutations and immune infiltrate densities or principal components.

Conclusions

Combining measures of immune infiltration provided improved survival modelling and evidence for the multiple effects of different immune factors on survival. The presence of stromal CD68⁺ and CD45RO⁺ populations was associated with survival, underscoring the benefits evaluating stromal immune populations may bring for prognostic immunoscores in HGSOC.

中文翻译：

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免疫浸润的联合测量显示出对高级别浆液性卵巢癌生存预测的叠加效应。

背景

在结直肠癌和乳腺癌中，免疫浸润的密度和定位提供了强有力的预后信息。我们询问类似的自动定量和免疫浸润的联合分析是否可以细化高级别浆液性卵巢癌（HGSOC）的预后信息，并测试了免疫反应模式与基因组驱动改变之间的关联。

方法

对上皮和基质进行半自动分割，并根据 332 个 HGSOC 患者组织微阵列核心的图像自动对 CD45RO ⁺、CD8 ⁺和 CD68 ^{+细胞的浸润进行定量。}

结果

上皮 CD8 [ p  = 0.027，风险比 (HR) = 0.83]、基质 CD68 ( p  = 3 × 10 ⁻⁴， HR = 0.44) 和基质 CD45RO ( p  = 7 × 10 ⁻⁴， HR = 0.76) 呈正相关与存活率有关，并且当对肿瘤和基质区室进行平均时仍然如此。通过主成分分析，我们结合了所有免疫标记物的信息，确定了优化的多参数生存模型（p  = 0.016，HR = 0.88）。PTEN 表达、 TP53突变类型或BRCA1/BRCA2突变的存在与免疫浸润密度或主要成分之间没有显着相关性。

结论

结合免疫浸润测量提供了改进的生存模型和不同免疫因素对生存的多重影响的证据。^{基质 CD68 +}和 CD45RO ⁺群体的存在与生存相关，强调了评估基质免疫群体可能为 HGSOC 的预后免疫评分带来的益处。