Huang Jing, Gong Qian, Li Qingshu, Xiao Ming, Li Ming, Zhang Shuxian, Wang Yalan, Tang Yi
Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.
Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University, Chongqing, 400016, China.
BMC Cancer. 2025 Aug 4;25(1):1267. doi: 10.1186/s12885-025-14660-5.
To explore the differences in tumor immune microenvironment between different KRAS mutation subtypes, and to provide a new direction for clinical immunotherapy of different subtypes of colorectal cancer.
We examined the spatial distribution of common inflammatory cell markers of CD8 + T cells, CD4 + T cells, natural killer cells, and B cells and macrophages in 55 colorectal cancer patients with different KRAS gene phenotypes using immunohistochemistry and panoramic scanning. We analyzed the relationship between inflammatory cells and clinical information. TCGA and String online databases were used to analyze the relationship between KRAS mutation subtypes and inflammatory cell markers.
We observed that significant differences in the spatial distribution of the tumor invasion front and the immune cell infiltration within the tumor. Colorectal cancer patients with different KRAS mutations showed different immune infiltration, and the main cells with differences were FOXP3 regulatory T cells and M2 macrophages. Furthermore, these two cell types were strongly associated with the prognosis of KRAS wild-type and KRAS mutant colorectal cancer.
The complexity of the immune microenvironment cannot be explained by infiltration of specific cell types alone, but may arise from cell-to-cell interactions or changes in the proportion of different immune cells. However, the infiltration of FOXP3 cells and M2 macrophages probably accounts for the differences between KRAS mutant subtypes.
探讨不同KRAS突变亚型之间肿瘤免疫微环境的差异，为不同亚型结直肠癌的临床免疫治疗提供新方向。
我们采用免疫组织化学和全景扫描技术，检测了55例具有不同KRAS基因表型的结直肠癌患者中CD8 + T细胞、CD4 + T细胞、自然杀伤细胞、B细胞和巨噬细胞等常见炎性细胞标志物的空间分布。我们分析了炎性细胞与临床信息之间的关系。利用TCGA和String在线数据库分析KRAS突变亚型与炎性细胞标志物之间的关系。
我们观察到肿瘤侵袭前沿的空间分布以及肿瘤内免疫细胞浸润存在显著差异。不同KRAS突变的结直肠癌患者表现出不同的免疫浸润，主要存在差异的细胞是FOXP3调节性T细胞和M2巨噬细胞。此外，这两种细胞类型与KRAS野生型和KRAS突变型结直肠癌的预后密切相关。
免疫微环境的复杂性不能仅用特定细胞类型的浸润来解释，而可能源于细胞间相互作用或不同免疫细胞比例的变化。然而，FOXP3细胞和M2巨噬细胞的浸润可能是KRAS突变亚型之间差异的原因。
