How tumor microenvironmental forces shape plasticity of cancer cell morphology is poorly understood. Here, we conduct automated histology image and spatial statistical analyses in 514 high grade serous ovarian samples to define cancer morphological diversification within the spatial context of the microenvironment. Tumor spatial zones, where cancer cell nuclei diversify in shape, are mapped in each tumor. Integration of this spatially explicit analysis with omics and clinical data reveals a relationship between morphological diversification and the dysregulation of DNA repair, loss of nuclear integrity, and increased disease mortality. Within the Immunoreactive subtype, spatial analysis further reveals significantly lower lymphocytic infiltration within diversified zones compared with other tumor zones, suggesting that even immune-hot tumors contain cells capable of immune escape. Our findings support a model whereby a subpopulation of morphologically plastic cancer cells with dysregulated DNA repair promotes ovarian cancer progression through positive selection by immune evasion.

中文翻译：

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微环境生态位散布塑造BRCA1失调的卵巢癌形态可塑性。

人们对肿瘤微环境力如何影响癌细胞形态的可塑性了解甚少。在这里，我们在514个高级别浆液性卵巢样本中进行了自动组织学图像和空间统计分析，以在微环境的空间范围内定义癌症的形态多样性。在每个肿瘤中都标有癌细胞核形状多样化的肿瘤空间区域。这种在空间上明确的分析与组学和临床数据的整合揭示了形态多样化与DNA修复失调，核完整性丧失和疾病死亡率增加之间的关系。在免疫反应性亚型中，空间分析进一步显示，与其他肿瘤区域相比，多样化区域内的淋巴细胞浸润明显降低，这表明即使是免疫热的肿瘤也含有能够免疫逃逸的细胞。我们的发现支持了一种模型，通过这种模型，形态学可塑性癌细胞的亚群具有失调的DNA修复，可通过免疫逃逸的阳性选择促进卵巢癌的进展。