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基于临床病理特征和血液指标预测结直肠癌患者原发性肿瘤微环境中免疫细胞浓度。

Immune cell concentrations among the primary tumor microenvironment in colorectal cancer patients predicted by clinicopathologic characteristics and blood indexes.

机构信息

VIP Department, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

出版信息

J Immunother Cancer. 2019 Jul 12;7(1):179. doi: 10.1186/s40425-019-0656-3.

Abstract

BACKGROUND

Immune cells play a key role in cancer progression and treatment. It is unclear whether the clinicopathologic characteristics and blood indexes of colorectal cancer (CRC) patients could predict immune cell concentrations in the tumor microenvironment.

METHODS

CRC patients with detailed data and tumor tissue who visited Sun Yat-sen University Cancer Center between April 1, 2004, and September 1, 2017, were enrolled. The densities of CD3+ and CD8+ T cells examined by immunohistochemistry in both the core of the tumor (CT) and the invasive margin (IM) were summed as the Immunoscore. The relationships between the Immunoscore and clinicopathologic characteristics and blood indexes, including tumor biomarkers (carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9)), inflammatory markers (lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin (ALB), neutrophils, lymphocytes, monocytes, platelets, NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and LMR (lymphocyte-to-monocyte ratio)) and lipid metabolism markers (cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB)), were analyzed using SPSS.

RESULTS

Older patients had lower CD3+ and CD8+ T cell expression in the IM and a lower Immunoscore than did younger patients. CD8+ T cell expression in the IM and the Immunoscore were lower in right-side tumors than in left-sided tumors. High CD8+ T cell expression in the CT was found in the T4 stage group. The higher the CEA level in the blood, the fewer CD8+ T cells were in the CT. Either fewer monocytes or a higher LMR in the blood, the larger number of CD3+ T cells in the CT. The more ApoA1 was in the blood, the more CD3+ T cells were in both the CT and the IM.

CONCLUSION

Age, T stage, tumor location, CEA, monocytes, LMR and ApoA1 could reflect immune cells infiltrating the tumor microenvironment of CRC.

摘要

背景

免疫细胞在癌症的发生和治疗中起着关键作用。目前尚不清楚结直肠癌(CRC)患者的临床病理特征和血液指标是否可以预测肿瘤微环境中免疫细胞的浓度。

方法

本研究纳入了 2004 年 4 月 1 日至 2017 年 9 月 1 日期间中山大学肿瘤防治中心就诊的详细数据和肿瘤组织的 CRC 患者。免疫组化检测肿瘤核心(CT)和浸润边缘(IM)的 CD3+和 CD8+T 细胞密度,将两者之和作为免疫评分(Immunoscore)。分析 Immunoscore 与临床病理特征和血液指标(包括肿瘤标志物[癌胚抗原(CEA)和糖类抗原 19-9(CA 19-9)]、炎症标志物[乳酸脱氢酶(LDH)、C 反应蛋白(CRP)、白蛋白(ALB)、中性粒细胞、淋巴细胞、单核细胞、血小板、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)和淋巴细胞与单核细胞比值(LMR)]和脂质代谢标志物[胆固醇(CHO)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、载脂蛋白 A1(ApoA1)和载脂蛋白 B(ApoB)])之间的关系,采用 SPSS 进行分析。

结果

与年轻患者相比,老年患者 IM 中 CD3+和 CD8+T 细胞的表达较低,免疫评分较低。右侧肿瘤 IM 中 CD8+T 细胞的表达和免疫评分低于左侧肿瘤。CT 中 CD8+T 细胞的表达在 T4 期组较高。血液中 CEA 水平越高,CT 中 CD8+T 细胞越少。血液中单核细胞越少或 LMR 越高,CT 中 CD3+T 细胞越多。血液中 ApoA1 越多,CT 和 IM 中 CD3+T 细胞越多。

结论

年龄、T 分期、肿瘤位置、CEA、单核细胞、LMR 和 ApoA1 可以反映 CRC 肿瘤微环境中浸润的免疫细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae3/6625045/a677869df3ac/40425_2019_656_Fig1_HTML.jpg

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