人子宫颈癌PD-L1的表达及其与肿瘤内浸润T细胞的相关性研究
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摘要
宫颈局部微环境免疫水平低下是宫颈癌发生发展的重要因素,且肿瘤内浸润的CD8+T细胞是宫颈癌独立的预后因素之一。T细胞的激活除了接受MHC分子提呈的肿瘤抗原外,还需要接受协同刺激信号。目前已知的协同刺激分子包括正向协同刺激分子如CD28,还包括负向协同刺激分子如程序性死亡配体1(programmed death ligand 1,PD-L1)。文献报道多种恶性肿瘤表达PD-L1,该分子与活化T细胞表达的程序性死亡1(programmed death-1,PD-1)结合抑制T细胞的增殖分化并导致T细胞凋亡。
本研究采用免疫组织化学染色观察人体5例正常宫颈组织、7例高级别宫颈上皮内瘤变(cervical intraepithelial neoplasiaⅡ-Ⅲ,CINⅡ-Ⅲ)组织和67例子宫颈癌组织PD-L1的表达和淋巴细胞PD-1的表达,免疫荧光染色观察了相应组织内浸润的CD4+T和CD8+T细胞数量,并通过TUNEL法检测了肿瘤内浸润淋巴细胞的凋亡情况。
研究结果显示正常子宫颈上皮不表达PD-L1;宫颈瘤变上皮不表达或弱阳性表达PD-L1,其相对积分光密度平均值为(0.82±0.75);70%(47/67)的宫颈癌表达PD-L1,浅表浸润(浸润深度<5mm)和深部浸润的宫颈鳞状细胞癌PD-L1的相对积分光密度平均值分别为(2.70±1.68)、(2.90±1.72)。CIN病灶和肿瘤内浸润的部分淋巴细胞表达PD-1。子宫颈瘤变上皮与子宫颈鳞状细胞癌PD-L1表达存在明显差异(P<0.01),浅表浸润的子宫颈鳞状细胞癌PD-L1的表达略低于深部浸润的鳞状细胞癌,但无统计学差异;PD-L1阳性病例肿瘤局部浸润的CD8+T细胞数量显著减少,且PD-L1表达与CD8+T细胞数量明显负相关(r=-0.82,P<0.01),但与肿瘤局部CD4+T细胞数量无明显相关性(r=-0.05,P>0.05);虽然原发灶内宫颈癌细胞表达PD-L1,但淋巴结转移灶内的宫颈癌细胞不表达PD-L1;部分PD-L1阳性的子宫颈癌局部浸润的淋巴细胞存在凋亡现象。
本研究结论:子宫颈癌细胞异常表达PD-L1,且PD-L1的表达与肿瘤局部浸润的CD8+T细胞数量减少有关,但与浸润的CD4+T细胞数量无关。癌细胞PD-L1的表达与其淋巴结转移无关。癌细胞可能通过PD-L1/PD-1途径促进了肿瘤内浸润的T淋巴细胞凋亡。
The low level of immunity in cervical microenvironment is an important factor in the genesis and progress of cervical cancer, Tumor infiltrating CD8+T is an independent prognostic factor in cervical cancer. The activation of T cells require the message from tumor antigen which presented by MHC molecules, and co-stimulating factor molecules, such as positive co-stimulating factor CD28 and negative co-stimulating factor programmed death ligand1. It was reported that multiple malignant tumors express PD-L1, which can combine with PD-1 of activated T cell, suppressed the proliferation and differentiation of T cells, and induced apoptosis of T cells.
In this paper, PD-L1 and PD-1 expression was respectively determined in five cases of normal cervical tissue, 7 cases of high-level cervical intraepithelial neoplasia (CINⅡ-Ⅲ) and 67 cases of cervical carcinomas of human by immunohistochemistry staining; the tumor infiltrating CD4+T and CD8+T cell were determined by immunofluorescent staining, and the apoptosis of tumor-infiltration lymphocytes was examined by TUNEL assay in those cases.
The results showed that no PD-L1 expressed in normal cervical epithelium; PD-L1 negatively or weakly expressed in epithelia of high grade CIN, the average relative optical density was (0.82±0.75); and PD-L1 expressed in 70% (47/67) cervical carcinomas, the average relative optical density in superficial infiltrating (<5mm) and deep infiltrating cervical squamous cell carcinomas was (2.70±1.68) and (2.90±1.72). PD-1 expressed in partial tumor-infiltrating lymphocytes in those cases. There was a significantly different PD-L1 expression between the epithelium of CIN and the cervical carcinomas (P < 0.01), PD-L1 expression density of superficial invasive cervical carcinomas was slightly lower than that of deep invasive cervical carcinomas, but there was no significant statistic difference between them. PD-L1 expression negatively associated with the number of tumor-infiltrating CD8+T cells (r =-0.82, P<0.01), but did not associate with the number of tumor-infiltrating CD4+T cells (r =-0.05, P> 0.05); cervical carcinoma cells in metastatic lymph node did not express PD-L1 although primary cervical carcinoma cells express PD-L1; apoptosis occurred in partial tumor-infiltrating lymphocytes in cervical carcinomas.
The study concludes that cervical carcinoma cells express PD-L1, and PD-L1 expression negatively associates with the number of tumor-infiltrating CD8+T cells, but do not associates with the number of tumor-infiltrating CD4+T cells. Lymph node metastatic cervical carcinoma cells dose not express PD-L1 although primary cervical carcinoma cells express PD-L1. PD-L1/PD-1 pathway may play role on apoptosis of tumor-infiltrating lymphocytes.
本研究采用免疫组织化学染色观察人体5例正常宫颈组织、7例高级别宫颈上皮内瘤变(cervical intraepithelial neoplasiaⅡ-Ⅲ,CINⅡ-Ⅲ)组织和67例子宫颈癌组织PD-L1的表达和淋巴细胞PD-1的表达,免疫荧光染色观察了相应组织内浸润的CD4+T和CD8+T细胞数量,并通过TUNEL法检测了肿瘤内浸润淋巴细胞的凋亡情况。
研究结果显示正常子宫颈上皮不表达PD-L1;宫颈瘤变上皮不表达或弱阳性表达PD-L1,其相对积分光密度平均值为(0.82±0.75);70%(47/67)的宫颈癌表达PD-L1,浅表浸润(浸润深度<5mm)和深部浸润的宫颈鳞状细胞癌PD-L1的相对积分光密度平均值分别为(2.70±1.68)、(2.90±1.72)。CIN病灶和肿瘤内浸润的部分淋巴细胞表达PD-1。子宫颈瘤变上皮与子宫颈鳞状细胞癌PD-L1表达存在明显差异(P<0.01),浅表浸润的子宫颈鳞状细胞癌PD-L1的表达略低于深部浸润的鳞状细胞癌,但无统计学差异;PD-L1阳性病例肿瘤局部浸润的CD8+T细胞数量显著减少,且PD-L1表达与CD8+T细胞数量明显负相关(r=-0.82,P<0.01),但与肿瘤局部CD4+T细胞数量无明显相关性(r=-0.05,P>0.05);虽然原发灶内宫颈癌细胞表达PD-L1,但淋巴结转移灶内的宫颈癌细胞不表达PD-L1;部分PD-L1阳性的子宫颈癌局部浸润的淋巴细胞存在凋亡现象。
本研究结论:子宫颈癌细胞异常表达PD-L1,且PD-L1的表达与肿瘤局部浸润的CD8+T细胞数量减少有关,但与浸润的CD4+T细胞数量无关。癌细胞PD-L1的表达与其淋巴结转移无关。癌细胞可能通过PD-L1/PD-1途径促进了肿瘤内浸润的T淋巴细胞凋亡。
The low level of immunity in cervical microenvironment is an important factor in the genesis and progress of cervical cancer, Tumor infiltrating CD8+T is an independent prognostic factor in cervical cancer. The activation of T cells require the message from tumor antigen which presented by MHC molecules, and co-stimulating factor molecules, such as positive co-stimulating factor CD28 and negative co-stimulating factor programmed death ligand1. It was reported that multiple malignant tumors express PD-L1, which can combine with PD-1 of activated T cell, suppressed the proliferation and differentiation of T cells, and induced apoptosis of T cells.
In this paper, PD-L1 and PD-1 expression was respectively determined in five cases of normal cervical tissue, 7 cases of high-level cervical intraepithelial neoplasia (CINⅡ-Ⅲ) and 67 cases of cervical carcinomas of human by immunohistochemistry staining; the tumor infiltrating CD4+T and CD8+T cell were determined by immunofluorescent staining, and the apoptosis of tumor-infiltration lymphocytes was examined by TUNEL assay in those cases.
The results showed that no PD-L1 expressed in normal cervical epithelium; PD-L1 negatively or weakly expressed in epithelia of high grade CIN, the average relative optical density was (0.82±0.75); and PD-L1 expressed in 70% (47/67) cervical carcinomas, the average relative optical density in superficial infiltrating (<5mm) and deep infiltrating cervical squamous cell carcinomas was (2.70±1.68) and (2.90±1.72). PD-1 expressed in partial tumor-infiltrating lymphocytes in those cases. There was a significantly different PD-L1 expression between the epithelium of CIN and the cervical carcinomas (P < 0.01), PD-L1 expression density of superficial invasive cervical carcinomas was slightly lower than that of deep invasive cervical carcinomas, but there was no significant statistic difference between them. PD-L1 expression negatively associated with the number of tumor-infiltrating CD8+T cells (r =-0.82, P<0.01), but did not associate with the number of tumor-infiltrating CD4+T cells (r =-0.05, P> 0.05); cervical carcinoma cells in metastatic lymph node did not express PD-L1 although primary cervical carcinoma cells express PD-L1; apoptosis occurred in partial tumor-infiltrating lymphocytes in cervical carcinomas.
The study concludes that cervical carcinoma cells express PD-L1, and PD-L1 expression negatively associates with the number of tumor-infiltrating CD8+T cells, but do not associates with the number of tumor-infiltrating CD4+T cells. Lymph node metastatic cervical carcinoma cells dose not express PD-L1 although primary cervical carcinoma cells express PD-L1. PD-L1/PD-1 pathway may play role on apoptosis of tumor-infiltrating lymphocytes.
引文
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