The Clinical and Biomarker Association of Programmed Death Ligand 1 and its Spatial Heterogeneous Expression in Colorectal Cancer

被引：16

作者：

Wei, Xiao-Li ^{[1
]}

Wu, Qi-Nian ^{[2
]}

Chen, Dong-Liang ^{[1
]}

Zeng, Zhao-Lei ^{[2
]}

Liu, Ze-Xian ^{[3
]}

Lu, Jia-Bin ^{[2
]}

Ju, Huai-Qiang ^{[2
]}

Ren, Chao ^{[1
]}

Pan, Zhi-Zhong ^{[4
]}

Wang, Feng-Hua ^{[1
]}

Xu, Rui-Hua ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Dept Med Oncol, Canc Ctr, State Key Lab Oncol South China,Collaborat Innova, 651 Dong Feng Rd East, Guangzhou 510060, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Pathol, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, Dept Colorectal Surg, State Key Lab Oncol South China,Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China

来源：

JOURNAL OF CANCER | 2018年 / 9卷 / 23期

关键词：

colorectal cancer; programmed death ligand 1; microsatellite instability; tumor-infiltrating immune cells; heterogeneity; PD-L1; EXPRESSION; ADVANCED MELANOMA; CELL; NIVOLUMAB; PEMBROLIZUMAB; LYMPHOCYTES; RELEVANCE; BLOCKADE;

D O I：

10.7150/jca.27735

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Programmed death ligand 1 (PD-L1) expression has been shown to predict benefit from anti-PD-1 treatment in several cancers. However, its predictive value in colorectal cancer seems limited. This study was aimed to explore the clinical and biomarker association of programmed death ligand 1 and its spatial heterogeneous expression in colorectal cancer. Methods: Tissue microarrays of 422 primary colorectal cancers from our hospital were used for the interpretation of PD-L1 and programmed death 1 (PD-1) expression, cluster of differentiation 4 (CD4) and CD8 density and microsatellite instability (MSI) status by immunohistochemistry. To assess the spatial heterogeneity of PD-L1 expression, Tissue microarrays of 383 paired intra-primary-tumor tissues, and 105 paired lymph node metastatic tumors and 64 paired distant metastatic tumors were also used. Results: PD-L1 was positive in 188 (44.5%) primary colorectal cancers. PD-L1 expression was associated with less advanced N category (P< 0.001), less advanced TNM stage (P< 0.001) and less nervous invasion (P= 0.04). Higher PD-L1 expression was associated with higher PD-1 expression (P< 0.001), higher CD4 (P< 0.001) and CD8 (P<0.001) density and DNA mismatch repair deficiency (P= 0.01). PD-L1 expression was associated with better disease-free survival and overall survival, but it was only an independent prognostic factor for disease-free survival (hazard ratio and 95% confidence interval: 0.42 [0.25-0.72], P< 0.001). The probability of inconsistent PD-L1 expression was respectively 17.8%, 31.4% and 39.1% within primary tumors, between primary tumors and lymph node metastatic tumors, and between primary tumors and distant metastatic tumors. All the three differences were statistically significant (P< 0.001, P< 0.001 and P= 0.05, respectively). Conclusions: PD-L1 expression was a marker of pre-existing immune responses in colorectal cancer, however, it was heterogeneously expressed in colorectal cancer, especially between primary and metastatic tumors. This might partially explain the low-efficiency of its predictive value for benefit from anti-PD-1 treatment.

引用

页码：4325 / 4333

页数：9

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