Department of Abdominal Surgery, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
Cancer Control. 2020 Jan-Dec;27(1):1073274820903383. doi: 10.1177/1073274820903383.
Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance.
Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients' survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration.
Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort.
Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.
分析肿瘤免疫浸润已被证明优于肿瘤、淋巴结、转移分期，可预测结直肠癌（CRC）的临床病程。表达 OX40（肿瘤坏死因子受体家族的一员）或 CD16（自然杀伤细胞、单核细胞和树突状细胞表达）的细胞浸润与 CRC 患者的良好预后相关。我们假设评估 CRC 中 OX40+和 CD16+细胞的浸润可能会产生增强的预后意义。
使用组织微阵列和特定抗体通过免疫组织化学检测 441 例原发性 CRC 中 OX40 和表达 CD16 的细胞的浸润情况。通过 Kaplan-Meier 和对数秩检验评估患者的生存情况。还使用多变量 Cox 回归分析、风险比和 95%置信区间来评估 OX40+和 CD16+细胞浸润的预后意义。
CRC 中 OX40+和 CD16+细胞的浸润分为 4 组，所有可能的组合均具有高或低的浸润水平。高水平的 OX40+和 CD16+细胞浸润与较低的 pT 分期、无肿瘤周围淋巴细胞浸润（PTL）炎症以及阳性预后相关。与其他组相比，具有高浸润水平的 CD16+和 OX40+细胞的肿瘤患者的总生存期也明显更长。这些结果通过分析独立的验证队列得到了证实。
OX40+和 CD16+免疫细胞的共同浸润是 CRC 的独立预后良好标志物。CD16+免疫细胞浸润的预后价值通过与 OX40+细胞浸润的联合分析得到显著改善。
