Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Cancer Immunol Immunother. 2020 Jul;69(7):1265-1277. doi: 10.1007/s00262-020-02545-4. Epub 2020 Mar 13.
Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRL) and without TRL (TRL) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRL and TRL tumors. The immunological profiles of patients in the TCGA database with high (LS) or low LS scores were compared. TRL tumors were transcriptionally distinct from TRL tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (n = 303), patients with high LS had inferior survival rates compared to those with low LS (P = 0.023). LS tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LS tumors also expressed higher levels of CXCR2 chemokines, CSF2, and CSF3. In the pan-cancer cohort (n = 9984), LS tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention.
肿瘤相关性白细胞增多症（TRL）与多种癌症的不良预后相关，但 TRL 相关人类肿瘤的微环境尚未完全阐明。在这里，我们旨在描述 TRL 相关癌症患者的免疫微环境。比较了宫颈癌患者肿瘤组织中伴有 TRL（TRL）和不伴 TRL（TRL）的转录特征。为了替代 TRL 诊断，我们使用 TRL 和 TRL 肿瘤之间差异表达的基因推导了白细胞增多症特征（LS）评分。比较了 TCGA 数据库中 LS 评分高（LS）或低 LS 评分患者的免疫谱。TRL 肿瘤与 TRL 肿瘤在转录水平上存在明显差异，表现为辐射抗性基因上调和适应性免疫反应相关基因下调。在 TCGA 宫颈癌队列（n=303）中，LS 评分高的患者与 LS 评分低的患者相比，生存率较低（P=0.023）。LS 肿瘤富含辐射抗性、伤口愈合和髓系来源抑制细胞（MDSC）特征，并且 M2 巨噬细胞浸润较高，M1 巨噬细胞和淋巴细胞浸润较低。LS 肿瘤还表达更高水平的 CXCR2 趋化因子、CSF2 和 CSF3。在泛癌队列（n=9984）中，LS 肿瘤也表现出较差的预后、抑制性免疫微环境特征和更高的 CXCR2 趋化因子表达。我们的数据为 TRL 患者存在抑制性免疫微环境提供了证据，并表明 CXCR2 轴等有希望的靶点可用于其治疗干预。
