Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients

Yusuke Omura, Yuji Toiyama, Yoshinaga Okugawa, Chengzeng Yin, Tsunehiko Shigemori, Kurando Kusunoki, Yukina Kusunoki, Shozo Ide, Tadanobu Shimura, Hiroyuki Fujikawa, Hiromi Yasuda, Junichiro Hiro, Masaki Ohi, Masato Kusunoki

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Background: Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear. Methods: We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulating sPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I–III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients. Results: Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival (OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serum sPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71–8.51, p = 0.001; HR 5.72, 95% CI 1.87–14.54, p = 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23–4.95, p = 0.01; HR 6.88, 95% CI 2.42–17.13, p = 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination. Conclusions: We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I–III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients.

Original languageEnglish
Pages (from-to)2533-2546
Number of pages14
JournalCancer Immunology, Immunotherapy
Issue number12
Publication statusPublished - 12-2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research


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