Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2017-07, Vol.66 (7), p.927-939
• Main Authors: Lee, Kyu Sang, Kwak, Yoonjin, Ahn, Soyeon, Shin, Eun, Oh, Heung-Kwon, Kim, Duck-Woo, Kang, Sung-Bum, Choe, Gheeyoung, Kim, Woo Ho, Lee, Hye Seung
• Format: Article
• Language: English
• Subjects: Aged; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Cancer Research; CD3 antigen; CD3 Complex - biosynthesis; CD8 antigen; CD8 Antigens - biosynthesis; Cell density; Cohort Studies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Female; Genetic Markers; Heterogeneity; Humans; Immunohistochemistry; Immunology; Immunotherapy; Kaplan-Meier Estimate; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medicine; Medicine & Public Health; Microsatellite Instability; Microsatellite Repeats; Middle Aged; Mismatch repair; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oncology; Original; Original Article; PD-L1 protein; Prognosis; Protein expression; Proteins; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins B-raf - metabolism; Raf protein; Tissue Array Analysis; Tumor cells; Tumor-infiltrating lymphocytes
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-017-1999-6

In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC. IHC slides stained for CD3 and CD8 were scanned using an Aperio ScanScope for precise calculation of tumor-infiltrating T cell density. Additionally, samples were screened for the B-Raf (BRAF)-V600E mutation using a Cobas 4800 System and IHC. In total, CD274 TC , CD274 TP , CD274 IC , and CD274 IP were observed in 43 (23.1%), 47 (25.3%), 107 (57.5%), and 102 (54.8%) of the MSI-H CRCs examined, and in three (2.0%), four (2.6%), 47 (30.7%), and 56 (36.6%) of the 153 MSS CRCs tested. Meanwhile, intratumoral heterogeneity of CD274 expression in tumor cells and immune cells was detected in 24 (12.9%) and 47 (25.3%) MSI-H CRCs, respectively. Notably, in both MSI-H and MSS CRC, CD274 IC and CD274 IP were independently associated with improved prognosis ( P