Ugai Tomotaka, Shimizu Takashi, Kawamura Hidetaka, Ugai Satoko, Takashima Yasutoshi, Usui Genki, Väyrynen Juha P, Okadome Kazuo, Haruki Koichiro, Akimoto Naohiko, Masugi Yohei, da Silva Annacarolina, Mima Kosuke, Zhang Xuehong, Chan Andrew T, Wang Molin, Garrett Wendy S, Freeman Gordon J, Meyerhardt Jeffrey A, Nowak Jonathan A, Song Mingyang, Giannakis Marios, Ogino Shuji
Program in MPE Molecular Pathological Epidemiology, Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USA.
Department of Epidemiology Harvard T.H. Chan School of Public Health Boston MA USA.
Clin Transl Immunology. 2023 Aug 2;12(8):e1453. doi: 10.1002/cti2.1453. eCollection 2023.
The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of . We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of in colorectal carcinoma.
We assessed tumor CD274 expression by immunohistochemistry and DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and , and mutations.
DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of in colorectal cancer tissue ( = 0.0077). For one category-unit increase in three ordinal categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41-1.51), 0.64 (0.32-1.28) and 0.50 (0.25-0.99), respectively ( = 0.032).
Tumor CD274 expression level was inversely associated with the amount of in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor enrichment) tend to be used by different tumor subgroups.
已知CD274（程序性细胞死亡1配体1，PD-L1）/PDCD1（程序性细胞死亡1，PD-1）免疫检查点轴可调节抗肿瘤免疫反应。也有证据支持……的免疫抑制作用。我们假设在结直肠癌中肿瘤CD274过表达可能与……丰度呈负相关。
在两项前瞻性队列研究中发生的4465例新发直肠癌和结肠癌病例中的812例中，我们通过免疫组织化学评估肿瘤CD274表达，并通过定量PCR评估肿瘤组织内的……DNA。由于组织数据可用性和潜在混杂因素（包括微卫星不稳定性状态、CpG岛甲基化表型、LINE-1甲基化水平以及……、……和……突变），使用具有逆概率加权的多变量逻辑回归分析来调整选择偏倚。
在109例（13%）病例的肿瘤组织中检测到……DNA。肿瘤CD274表达水平与结直肠癌组织中的……量呈负相关（……=0.0077）。对于三个有序……类别（阴性vs.低vs.高）中一个类别单位的增加，低、中和高CD274类别（vs.阴性）的多变量调整优势比（95%置信区间）分别为0.78（0.41 - 1.51）、0.64（0.32 - 1.28）和0.50（0.25 - 0.99）（……=0.032）。
肿瘤CD274表达水平与结直肠癌组织中的……量呈负相关，表明不同的肿瘤亚组倾向于使用不同的免疫抑制机制（即PDCD1免疫检查点激活和肿瘤……富集）。
