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

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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 CD274IP 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, CD274IC and CD274IP were 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.

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Abbreviations

AJCC:

American Joint Committee on Cancer

C:

Center

CI:

Confidence interval

CRC:

Colorectal cancer

FFPE:

Formalin-fixed and paraffin-embedded

HR:

Hazard ratio

IC:

Immune cells at the center

IHC:

Immunohistochemistry

IP:

Immune cells at the periphery

LS:

Lynch syndrome

MSI-H:

Microsatellite instability-high

MSS:

Microsatellite stable

P:

Periphery

PCR:

Polymerase chain reaction

PD-1:

Programmed cell death 1

PD-L1:

Programmed cell death ligand 1

TC:

Tumor cells at the center

TP:

Tumor cells at the periphery

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Authors and Affiliations

  1. Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea

    Kyu Sang Lee, Yoonjin Kwak, Eun Shin, Gheeyoung Choe & Hye Seung Lee

  2. Medical Research Collaborating Center, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea

    Soyeon Ahn

  3. Department of Surgery, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea

    Heung-Kwon Oh, Duck-Woo Kim & Sung-Bum Kang

  4. Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro (Yongon-dong), Jongno-gu, Seoul, 110-799, Republic of Korea

    Gheeyoung Choe, Woo Ho Kim & Hye Seung Lee

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  1. Kyu Sang Lee
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Correspondence to Hye Seung Lee.

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This research was supported by a Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Education, Republic of Korea (NRF-2016R1D1A1B03931744).

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Lee, K.S., Kwak, Y., Ahn, S. et al. Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer. Cancer Immunol Immunother 66, 927–939 (2017). https://doi.org/10.1007/s00262-017-1999-6

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