王月娇　　史学森　　白雪峰

[摘要] 目的 探討结直肠癌中CD4+T、CD8+T细胞和PD-L1的表达情况，并分析其相关性及临床病理学意义。 方法 收集2019年1—12月包头市肿瘤医院手术切除的结直肠癌肿物及癌旁5 cm、10 cm石蜡组织标本各41例，免疫组化法检测CD4+T、CD8+T细胞和PD-L1的表达水平，Sanger测序法检测微卫星不稳定性。 结果 结直肠癌癌组织CD4+T细胞表达阳性的细胞数为108.8个，高于癌旁5 cm的73.8个及癌旁10 cm的38.0个，差异有统计学意义（P<0.05）;癌组织CD8+T细胞表达阳性的细胞数为63.8个，高于癌旁5 cm的33.8个及癌旁10 cm的22.4个，差异有统计学意义（P<0.05）;癌组织PD-L1表达阳性的细胞数为18.0个，高于癌旁5 cm的3.2个及癌旁10 cm的1.2个，差异有统计学意义（P<0.05）。神经侵犯、脉管癌栓与结直肠癌癌组织CD4+T细胞表达相关，MSI、淋巴结转移、脉管癌栓与CD8+T细胞表达有关，MSI、淋巴结转移、神经侵犯、脉管癌栓与PD-L1的表达均无关。PD-L1和CD8+T细胞的表达呈低度正相关（r=0.350，P<0.05），PD-L1与CD4+T细胞表达无相关性（r=0.138，P>0.05）。 结论 CD4+T、CD8+T细胞和PD-L1在癌组织高表达，CD8+T与CD4+T细胞两者的高表达可作为预后良好的辅助判断指标，PD-L1与CD8+T细胞表达呈正相关。

[关键词] 结直肠癌;CD4+T细胞;CD8+T细胞;PD-L1;微卫星不稳定性

[中图分类号] R735.35          [文献标识码] B          [文章编号] 1673-9701（2021）09-0152-04

The expression and significance of CD4+T， CD8+T cell and PD-L1 in colorectal cancer

WANG Yuejiao1   SHI Xuesen2   BAI Xuefeng3

1.Graduate School of Baotou Medical College， Baotou  014040， China; 2.Baotou Center for Disease Control and Prevention in Inner Mongolla Autonomous Region， Baotou  014030， China; 3.Department of Pathology， Baotou Cancer Hospital in Inner Mongolla Autonomous Region， Baotou  014030， China

[Abstract] Objective To investigate the expression of CD4+T cells， CD8+T cells and PD-L1 in colorectal cancer， and to analyze their correlation and clinicopathological significance. Methods 41 cases of colorectal cancer tumors and paraffin tissue specimens 5 cm and 10 cm adjacent to the cancer were collected from Baotou Cancer Hospital from January to December 2019. The expression levels of CD4+T， CD8+T cells and PD-L1 were detected by immunohistochemistry， and the microsatellite instability was detected by sanger sequencing method. Results The number of CD4+T cells in colorectal cancer tissues was 108.8， which was higher than 73.8 cells in 5 cm adjacent to cancer and 38.0 cells in 10 cm adjacent to cancer， and the difference was statistically significant（P<0.05）. The number of CD8+ T cells in cancer tissue was 63.8， which was higher than 33.8 in 5 cm and 22.4 in 10 cm adjacent to cancer（P<0.05）; The number of PD-L1 positive cells in cancer tissue was 18.0， which was higher than 3.2 in 5 cm and 1.2 in 10 cm adjacent to cancer（P<0.05）. MSI， lymph node metastasis and vascular tumor thrombus were related to the expression of CD8+T cells. MSI， lymph node metastasis， nerve invasion and vascular tumor thrombus were not related to the expression of PD-L1. There was a low positive correlation between the expression of PD-L1 and CD8+T cells（r=0.350， P<0.05）， but no correlation between the expression of PD-L1 and CD4+T cells（r=0.138， P>0.05）. Conclusion CD4+T cells， CD8+T cells， and PD-L1 are highly expressed in cancer tissues. The high expression of CD8+T cells and CD4+T cells can be used as auxiliary indicators for a good prognosis. The expression of PD-L1 is positively related to CD8+T cells.

[Key words] Colorectal cancer; CD4+T cells; CD8+T cells; PD-L1; Microsatellite instability

结直肠癌（Colorectal cancer，CRC）是一种常见的胃肠道恶性肿瘤，其发病率在所有恶性肿瘤中位居第三位[1]。近年来CRC的死亡率明显上升，因此深入研究并寻找新的治疗策略意义重大。肿瘤浸润淋巴细胞（Tumor infiltrating lymphocytes，TIL）是肿瘤细胞免疫的重要组分，CD8+T细胞是主要的抗肿瘤效应细胞，CD4+T细胞则促进其活化增殖，二者协同可对抗肿瘤。程序性死亡因子-1（Programmmed death-1，PD-1）/程序性死亡因子配体-1（Programmmed death ligand-1，PD-L1）属负性刺激分子，可诱导T细胞衰竭，促进肿瘤进展[2]。目前PD-L1的抗体阻断治疗已在微卫星不稳定（Microsatellite instability，MSI）型CRC中取得较为可观的疗效。但前期研究中PD-L1与CD4+T细胞、CD8+T细胞的关系分析却少有报道。本研究旨在检测CRC癌组织和癌旁组织中CD4+T、CD8+T细胞和PD-L1的表达水平，并分析其相关性及意义，为CRC的预后判断及免疫治疗提供理论依据，现报道如下。

1 资料与方法

1.1 一般资料

收集2019年1—12月包头市肿瘤医院手术切除的CRC肿物及癌旁5 cm、10 cm石蜡组织标本各41例，均为首次切除，且无结直肠免疫相关病史，术前亦未行放化疗或生物免疫治疗。……