FABP6 表达与结直肠癌细胞中的免疫浸润和免疫原性相关。
FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells.
机构信息
Department of Clinical Laboratory, Henan Provincial Third People's Hospital, Zhengzhou, 450006 Henan, China.
Department of Neurology, Henan Provincial Third People's Hospital, Zhengzhou, 450006 Henan, China.
出版信息
J Immunol Res. 2022 Aug 17;2022:3129765. doi: 10.1155/2022/3129765. eCollection 2022.
BACKGROUND
Immune checkpoint inhibitors (ICIs) have rapidly revolutionized colorectal cancer (CRC) treatment, but resistance caused by the heterogeneous tumor microenvironment (TME) still presents a challenge. Therefore, it is necessary to characterize TME immune infiltration and explore new targets to improve immunotherapy.
METHODS
The compositions of 64 types of infiltrating immune cells and their relationships with CRC patient clinical characteristics were assessed. Differentially expressed genes (DEGs) between "hot" and "cold" tumors were used for functional analysis. A prediction model was constructed to explore the survival of CRC patients treated with and without immunotherapy. Finally, fatty acid-binding protein (FABP6) was selected for in vitro experiments, which revealed its roles in the proliferation, apoptosis, migration, and immunogenicity of CRC tissues and cell lines.
RESULTS
The infiltration levels of several immune cells were associated with CRC tumor stage and prognosis. Different cell types showed the synergistic or antagonism infiltration patterns. Enrichment analysis of DEGs revealed that immune-related signaling was significantly activated in hot tumors, while metabolic process pathways were altered in cold tumors. In addition, the constructed model effectively predicted the survival of CRC patients treated with and without immunotherapy. FABP6 knockdown did not significantly alter tumor cell proliferation, apoptosis, and migration. FABP6 was negatively correlated with immune infiltration, and knockdown of FABP6 increased major histocompatibility complex (MHC) class 1 expression and promoted immune-related chemokine secretion, indicating the immunogenicity enhancement of tumor cells. Finally, knockdown of FABP6 could promote the recruitment of CD8+ T cells.
CONCLUSION
Collectively, we described the landscape of immune infiltration in CRC and identified FABP6 as a potential immunotherapeutic target for treatment.
背景
免疫检查点抑制剂（ICIs）迅速改变了结直肠癌（CRC）的治疗方法，但由于异质性肿瘤微环境（TME）导致的耐药性仍然是一个挑战。因此，有必要对 TME 免疫浸润进行特征描述，并探索新的靶点以改善免疫治疗。
方法
评估了 64 种浸润免疫细胞的组成及其与 CRC 患者临床特征的关系。使用“热”肿瘤和“冷”肿瘤之间的差异表达基因（DEGs）进行功能分析。构建预测模型以探索接受和未接受免疫治疗的 CRC 患者的生存情况。最后，选择脂肪酸结合蛋白（FABP6）进行体外实验，揭示其在 CRC 组织和细胞系增殖、凋亡、迁移和免疫原性中的作用。
结果
几种免疫细胞的浸润水平与 CRC 肿瘤分期和预后相关。不同的细胞类型表现出协同或拮抗的浸润模式。DEGs 的富集分析表明，热肿瘤中免疫相关信号显著激活，而冷肿瘤中代谢过程途径发生改变。此外，构建的模型有效地预测了接受和未接受免疫治疗的 CRC 患者的生存情况。FABP6 敲低并未显著改变肿瘤细胞的增殖、凋亡和迁移。FABP6 与免疫浸润呈负相关，敲低 FABP6 增加了主要组织相容性复合体（MHC）I 类表达并促进了免疫相关趋化因子的分泌，表明肿瘤细胞的免疫原性增强。最后，敲低 FABP6 可以促进 CD8+T 细胞的募集。
结论
综上所述，我们描述了 CRC 中免疫浸润的全景，并确定 FABP6 作为一种潜在的免疫治疗靶点用于治疗。
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