Zhejiang Provincial Center for Disease Control and Prevention, Institute of Immunization and Prevention, Hangzhou, China.
Aging (Albany NY). 2023 Mar 13;15(5):1685-1698. doi: 10.18632/aging.204583.
The cervical cancer tumor microenvironment is a diverse and complex ecosystem. Tumor-immune cell infiltration (ICI) may influence immune escape and immunotherapeutic responses. However, the relationship between immune cell infiltrations, immune escape, and immunotherapy in cervical cancer has not been fully clarified. Here, Principal component analysis (PCA) and Tumor immune dysfunction and exclusion (TIDE) were applied to calculate individual ICI scores and probabilities of immune escape, respectively. Through the IMvigor210 and the Cancer Immunome Atlas (TCIA) datasets, we validated the different responses to immunotherapy in two subgroups of patients. Furthermore, therapeutic benefits of different patients were predicted by the pRRophetic package. We found that patients with high ICI scores were prone to immune escape due to the activated JAK-STAT signaling pathway, along with lower CD8+ T cells. High ICI scores patients could benefit more from anti-PD-L1 immunotherapy, and individuals with low scores may be better candidates for the anti-CTLA-4 treatment. Combinations of immunotherapies with targeted inhibitors may improve clinical efficacy and reduce the risk of tumor recurrence. The ICI model not only helps us enhance the cognition of immune escape, but also guides the application of immunotherapy in cervical cancer patients.
宫颈癌肿瘤微环境是一个多样化且复杂的生态系统。肿瘤免疫细胞浸润（ICI）可能会影响免疫逃逸和免疫治疗反应。然而，宫颈癌中免疫细胞浸润、免疫逃逸和免疫治疗之间的关系尚未完全阐明。在这里，我们分别应用主成分分析（PCA）和肿瘤免疫功能障碍和排斥（TIDE）来计算个体的 ICI 评分和免疫逃逸概率。通过 IMvigor210 和癌症免疫图谱（TCIA）数据集，我们验证了两组患者对免疫治疗的不同反应。此外，我们还通过 pRRophetic 包预测了不同患者的治疗获益。我们发现，由于激活的 JAK-STAT 信号通路和 CD8+T 细胞减少，高 ICI 评分的患者更容易发生免疫逃逸。高 ICI 评分的患者可能从抗 PD-L1 免疫治疗中获益更多，而低评分的患者可能更适合抗 CTLA-4 治疗。免疫治疗与靶向抑制剂的联合可能会提高临床疗效并降低肿瘤复发的风险。ICI 模型不仅有助于我们增强对免疫逃逸的认知，还指导了宫颈癌患者免疫治疗的应用。
