Wang Qianyu, Zhong Wentao, Xiao Yi, Lin Guole, Lu Junyang, Xu Lai, Zhang Guannan, Liu Aijun, Du Junfeng, Wu Bin
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Medical Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Cancer Sci. 2025 Feb;116(2):350-366. doi: 10.1111/cas.16400. Epub 2024 Nov 27.
The pan-immune-inflammation value reflects the systemic inflammatory response, and tumor-infiltrating lymphocytes indicate a local immune response in rectal cancer. However, the association between systemic inflammatory response, as indicated by the pan-immune-inflammation value, and local immune responses in rectal cancer remains unclear. This study analyzed 915 treatment-naïve rectal cancer patients from the Peking Union Medical College Hospital and PLA General Hospital (PLAGH) cohorts who underwent radical surgery to investigate the relationship between the pan-immune-inflammation value and immune responses. Lower pan-immune-inflammation value was significantly associated with improved disease-free survival and cancer-specific survival. Multivariate Cox regression models identified the pan-immune-inflammation value as an independent prognostic factor. In the PLAGH cohort, patients with low pan-immune-inflammation values had higher immune cell levels, activated immune pathways, and increased expression of immune checkpoint genes according to RNA sequencing. Hematoxylin and eosin staining and immunohistochemical analysis revealed that lower pan-immune-inflammation value was associated with higher tumor-infiltrating lymphocyte density, more mature tertiary lymphoid structures, increased CD8 T cells, and elevated human lymphocyte antigen class I expression. Conversely, patients with high pan-immune-inflammation values exhibited pathways linked to tumor progression, such as angiogenesis, epithelial-mesenchymal transition, hypoxia, KRAS signaling, and TGF-ß signaling. Among patients receiving anti-PD-1 therapy, responders had low pre- and post-treatment pan-immune-inflammation values. The pan-immune-inflammation value is a reliable marker associated with distinct immune microenvironment characteristics and can effectively predict disease-free survival, cancer-specific survival, and response to immunotherapy.
泛免疫炎症值反映全身炎症反应，而肿瘤浸润淋巴细胞表明直肠癌存在局部免疫反应。然而，泛免疫炎症值所指示的全身炎症反应与直肠癌局部免疫反应之间的关联仍不清楚。本研究分析了来自北京协和医院和中国人民解放军总医院（301 医院）队列的 915 例未经治疗的直肠癌患者，这些患者接受了根治性手术，以研究泛免疫炎症值与免疫反应之间的关系。较低的泛免疫炎症值与无病生存期和癌症特异性生存期的改善显著相关。多变量 Cox 回归模型将泛免疫炎症值确定为独立的预后因素。在 301 医院队列中，根据 RNA 测序，泛免疫炎症值低的患者免疫细胞水平较高、免疫途径激活且免疫检查点基因表达增加。苏木精和伊红染色以及免疫组织化学分析显示，较低的泛免疫炎症值与较高的肿瘤浸润淋巴细胞密度、更成熟的三级淋巴结构、CD8 T 细胞增加以及人类淋巴细胞抗原 I 类表达升高相关。相反，泛免疫炎症值高的患者表现出与肿瘤进展相关的途径，如血管生成、上皮-间质转化、缺氧、KRAS 信号传导和 TGF-β信号传导。在接受抗 PD-1 治疗的患者中，反应者治疗前和治疗后的泛免疫炎症值均较低。泛免疫炎症值是一种与不同免疫微环境特征相关的可靠标志物，可有效预测无病生存期、癌症特异性生存期和免疫治疗反应。
