Zou Ruanmin, Gu Ruihong, Yu Xia, Hu Yingying, Yu Junhui, Xue Xiangyang, Zhu Xueqiong
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, People's Republic of China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, People's Republic of China.
J Cancer. 2021 Apr 20;12(12):3501-3514. doi: 10.7150/jca.55970. eCollection 2021.
The role of infiltrating immune cells within the tumor microenvironment has received considerable attention, but their function in cervical cancer remains to be elucidated; thus, comprehensive evaluation of their predictive value is needed. Using cervical cancer samples from 406 patients, immune cell infiltration was evaluated via immunohistochemistry. CD3+, CD4+, CD8+, CD20+, CD57+, CD68+, and CD163+ cell infiltration was compared in samples from adjacent tissues and the tumor center. The associations between immune cell distributions in the tumor center, clinicopathological features, and prognosis were correlated among immune cell types. Using three immune features, an immune model was constructed based on a Cox regression analysis with the least absolute shrinkage and selection operator (lasso) penalty to derive immune risk scores. Immune cells that infiltrated the tumor center correlated with clinicopathological characteristics and prognosis. The immune risk scores were an independent prognostic indicator and were found to predict cervical cancer prognosis as well as the effects of chemoradiotherapy. We classified patients into either high- or low-risk subgroups (namely CD4+CD163+CD57+ and CD4+CD163+CD57+, respectively) based on their immune scores. Significant differences were found in the 3-year overall survival of patients with high- and low-risk scores (83.0% vs. 96.6%; < 0.001). High immune risk scores resulted in decreased overall survival for patients in stages IB1+IIA1, IB2+IIA2, and IIB-IV ( = 0.001, = 0.008, and = 0.044, respectively). Overall survival was significantly worse following chemoradiotherapy in high-scoring patients in stages IB1+IIA1 and IB2+IIA2 ( = 0.001 and =0.008, respectively). Moreover, overall survival was significantly worse after radiotherapy or chemotherapy in high-scoring patients in stage IB1+IIA1 ( = 0.03). Our work reveals that the distribution of infiltrating immune cells affects their function in cervical cancer. Our tumor center-centric immune model effectively predicted survival, suggesting its potential use in identifying suitable candidates for chemoradiotherapy.
肿瘤微环境中浸润性免疫细胞的作用已受到广泛关注，但其在宫颈癌中的功能仍有待阐明；因此，需要对其预测价值进行全面评估。利用406例患者的宫颈癌样本，通过免疫组织化学评估免疫细胞浸润情况。比较了相邻组织和肿瘤中心样本中CD3 +、CD4 +、CD8 +、CD20 +、CD57 +、CD68 +和CD163 +细胞的浸润情况。分析了肿瘤中心免疫细胞分布、临床病理特征和预后之间的相关性。利用三个免疫特征，基于Cox回归分析和最小绝对收缩与选择算子（lasso）惩罚构建免疫模型，以得出免疫风险评分。浸润到肿瘤中心的免疫细胞与临床病理特征和预后相关。免疫风险评分是一个独立的预后指标，可预测宫颈癌预后以及放化疗效果。根据免疫评分将患者分为高风险或低风险亚组（分别为CD4 + CD163 + CD57 +和CD4 + CD163 + CD57 +）。高风险和低风险评分患者的3年总生存率存在显著差异（83.0%对96.6%；P < 0.001）。高免疫风险评分导致IB1 + IIA1期、IB2 + IIA2期和IIB - IV期患者的总生存率降低（分别为P = 0.001、P = 0.008和P = 0.044）。IB1 + IIA1期和IB2 + IIA2期高评分患者放化疗后的总生存率显著更差（分别为P = 0.001和P = 0.008）。此外，IB1 + IIA1期高评分患者放疗或化疗后的总生存率也显著更差（P = 0.03）。我们的研究表明，浸润性免疫细胞的分布影响其在宫颈癌中的功能。我们以肿瘤中心为核心的免疫模型有效地预测了生存率，表明其在识别放化疗合适候选者方面的潜在用途。
