原句结构不变： 原发性结直肠癌患者强烈的免疫反应与以基质微环境为主的肿瘤相比，在手术后与存活率更好相关。然而，用于鉴定具有手术治疗后肝转移结直肠癌（CRLM）良好预后的生物标志物仍然无法确定。该研究的目的是确定免疫细胞浸润和基质含量的简单组织学评估在预测原发性结直肠癌和CRLM同步切除后的预后方面的实际应用，并探究推动疾病进展的潜在功能生物学。通过组织学评估、面板基因组学和批量转录组学评估、免疫组化和GeoMx空间转录学（ST）分析，详细评估了进行原发性结直肠癌和CRLM同步切除术的患者的样本。具有高度免疫细胞浸润的转移灶与改善的癌症特异性生存相关联。批量转录组学分析受基质含量干扰，但ST证明了长期存活者的转移灶侵袭边缘以适应性免疫细胞种群为特征，丰富了二型干扰素信号和MHC 2类抗原呈递。相比之下，预后不佳的患者表现出调节性T细胞和中性粒细胞增加，与Notch和TGFβ信号通路在转移性肿瘤中的富集相一致。总之，组织学评估可以对进行CRLM同步切除的患者的结果进行分层，表明它具有潜在的预测生物标志物的潜力。此外，ST分析揭示了显著的肿瘤内和病变间异质性，并确定了驱动每种表型的转录计划。空间转录组学揭示了结直肠癌反应性和被抑制免疫微环境之间的异质性。©2023作者；美国癌症研究协会出版。

Strong immune responses in primary colorectal cancer correspond with better patient survival following surgery compared with tumors with predominantly stromal microenvironments. However, biomarkers to identify patients with colorectal cancer liver metastases (CRLM) with good prognosis following surgery for oligometastatic disease remain elusive. The aim of this study was to determine the practical application of a simple histological assessment of immune cell infiltration and stromal content in predicting outcome following synchronous resection of primary colorectal cancer and CRLM and to interrogate the underlying functional biology that drives disease progression. Samples from patients undergoing synchronous resection of primary colorectal cancer and CRLM were evaluated in detail through histological assessment, panel genomic and bulk transcriptomic assessment, IHC, and GeoMx spatial transcriptomics (ST) analysis. High immune infiltration of metastases was associated with improved cancer-specific survival. Bulk transcriptomic analysis was confounded by stromal content, but ST demonstrated that the invasive edge of the metastases of long-term survivors was characterized by adaptive immune cell populations enriched for type II IFN signaling and MHC-class II antigen presentation. In contrast, patients with poor prognosis demonstrated increased abundance of regulatory T cells and neutrophils with enrichment of Notch and TGFβ signaling pathways at the metastatic tumor center. In summary, histological assessment can stratify outcomes in patients undergoing synchronous resection of CRLM, suggesting that it has potential as a prognostic biomarker. Furthermore, ST analysis has revealed significant intratumoral and interlesional heterogeneity and identified the underlying transcriptomic programs driving each phenotype.Spatial transcriptomics uncovers heterogeneity between patients, between matched lesions in the same patient, and within individual lesions and identifies drivers of metastatic progression in colorectal cancer with reactive and suppressed immune microenvironments.©2023 The Authors; Published by the American Association for Cancer Research.