title: Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer.
abstract: 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, CD274TC, CD274TP, CD274IC, and CD274IPwere 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, CD274ICand CD274IPwere independently associated with improved prognosis (P < 0.05), while BRAF mutation was associated with CD274TP, poor differentiation, sporadic type, and hMLH1(-)/hMSH2(+)/hMSH6(+)/PMS2(-) in MSI-H CRC (P < 0.006). In conclusion, CD274 expression in tumor-infiltrating immune cells was an independent factor for improved prognosis in CRC patients. A deeper understanding of CD274 status may yield improved responses to future CRC immunotherapies.
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.
authors.forename: Yoonjin
authors.initials: Y
authors.lastname: Kwak
authors.affiliation: Medical Research Collaborating Center, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.
authors.forename: Eun
authors.initials: E
authors.lastname: Shin
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.
authors.forename: Heung-Kwon
authors.initials: HK
authors.lastname: Oh
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Kang
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea.|Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro (Yongon-dong), Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Gheeyoung
authors.initials: G
authors.lastname: Choe
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro (Yongon-dong), Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea. hye2@snu.ac.kr.|Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro (Yongon-dong), Jongno-gu, Seoul, 110-799, Republic of Korea. hye2@snu.ac.kr.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D017252:CD3 Complex / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D017252:CD3 Complex; D016827:CD8 Antigens; D005819:Genetic Markers; D009363:Neoplasm Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: CD274; Colorectal cancer; Microsatellite instability; PD-L1; Prognosis; Tumor-infiltrating immune cells