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Journal of Cancer Research and Clinical Oncology

, Volume 144, Issue 6, pp 1005–1014 | Cite as

CD274, LAG3, and IDO1 expressions in tumor-infiltrating immune cells as prognostic biomarker for patients with MSI-high colon cancer

  • Soo Jung Lee
  • Sun-Young Jun
  • In Hee Lee
  • Byung Woog Kang
  • Su Yeon Park
  • Hye Jin Kim
  • Jun Seok Park
  • Gyu-Seog Choi
  • Ghilsuk Yoon
  • Jong Gwang Kim
Original Article – Cancer Research
  • 519 Downloads

Abstract

Purpose

This study attempted to reveal the prognostic impact of microsatellite instability-high (MSI-H) colon cancer with tumor-infiltrating immune cells (TIICs) and immune checkpoint protein expression, which are good candidates for immunotherapy.

Materials and methods

The study included 89 patients with MSI-H colon cancer who underwent curative surgery at Kyungpook National University Chilgok Hospital. The expression status of specific inhibitory receptors, such as CD274 (programmed death-ligand 1, PD-L1), PDCD1 (programmed cell death 1, PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and indolamine 2′3′-dioxygenase 1 (IDO1), was retrospectively analyzed using immunohistochemistry (IHC).

Results

Among the 89 patients, CD274, LAG3, and IDO1 expressions in TIICs were observed in 68.6% (61 cases), 13.5% (12), and 28.1% (25) of patients, respectively. Meanwhile, CD274, CTLA4, and IDO1 were expressed in tumor cells of 24.7% (22 cases), 4.5% (4), and 72.0% (64) of patients, respectively. During the median follow-up duration of 39 months, 14 (15.7%) patients experienced disease recurrence. Among the five immune checkpoint proteins, CD274, LAG3, and IDO1 expressions in TIICs were significantly associated with a better disease-free survival (DFS) in a univariate analysis (P = 0.028, 0.037, and 0.030 respectively). Moreover, co-expression of CD274, LAG3, and IDO1 in TIICs showed an even better survival for DFS (P = 0.010). In a multivariate survival analysis, CD274, LAG3, and IDO1 expressions in TIICs remained as independent prognostic factors for a better DFS.

Conclusion

CD274, LAG3, and IDO1 expressions in TIICs showed a better prognosis for patients with MSI-H colon cancer. Thus, the potential therapeutic implications of these immune checkpoint molecules should be further investigated.

Keywords

Colorectal cancer Microsatellite instability Tumor-infiltrating immune cells Immune checkpoint molecules Prognosis 

Notes

Funding

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (2014R1A5A2009242).

Compliance with ethical standards

Conflict of interest

The authors declared no conflicts of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Kyungpook National University Hospital Institutional Review Board (IRB).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

432_2018_2620_MOESM1_ESM.tif (215 kb)
Supplementary material 1 Supplementary Fig.1. Kaplan–Meier survival curves for disease-free survival according to the immune checkpoint proteins, CD274 (PD-L1), CTLA4, and IDO1 expression in tumor cells identified. (a) CD274 (T). (b) CTLA4 (T). (c) IDO1 (T). P values were calculated according to log-rank test. (TIF 214 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Soo Jung Lee
    • 1
    • 5
  • Sun-Young Jun
    • 2
  • In Hee Lee
    • 1
    • 5
  • Byung Woog Kang
    • 1
    • 5
  • Su Yeon Park
    • 3
    • 5
  • Hye Jin Kim
    • 3
    • 5
  • Jun Seok Park
    • 3
    • 5
  • Gyu-Seog Choi
    • 3
    • 5
  • Ghilsuk Yoon
    • 4
    • 5
  • Jong Gwang Kim
    • 1
    • 5
  1. 1.Department of Oncology/HematologyKyungpook National University HospitalDaeguSouth Korea
  2. 2.Department of PathologyIncheon St. Mary’s Hospital, The Catholic University of KoreaIncheonSouth Korea
  3. 3.Department of SurgeryKyungpook National University Medical HospitalDaeguSouth Korea
  4. 4.Department of PathologyKyungpook National University HospitalDaeguSouth Korea
  5. 5.School of MedicineKyungpook National UniversityDaeguSouth Korea

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