The prognostic effects of tumor infiltrating regulatory T cells and myeloid derived suppressor cells assessed by multicolor flow cytometry in gastric cancer patients

Abstract

// Han Sol Choi 1, 2, * , Sang Yun Ha 3, * , Hye-Mi Kim 1, 2 , Soo Min Ahn 3 , Myung-Soo Kang 4, 5 Kyoung-Mee Kim 3 , Min Gew Choi 6 , Joon Ho Lee 6 , Tae Sung Sohn 6 , Jae Moon Bae 6 , Sung Kim 6 , Eun-Suk Kang 2 1 Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 3 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Samsung Biomedical Research Institute (SBRI), Center for Future Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 6 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea * These author contributed equally to this work Correspondence to: Eun-Suk Kang, e-mail: eskang@skku.edu Kyoung-Mee Kim, e-mail: kkmkys@skku.edu Keywords: regulatory T cells, myeloid derived suppressor cells, prognosis, gastric cancer Received: April 17, 2015      Accepted: December 26, 2015      Published: January 20, 2016 ABSTRACT The prognostic effects of tumor infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs) and myeloid derived suppressing cells (MDSCs) are inconclusive in gastric cancers. We investigated the frequencies of TILs including CD8+ T cells, CD45+CD4+CD25± FOXP3+ Tregs, CD45+CD11b+ CD14+ HLA−DR− MDSCs in 28 gastric cancer tissues by using multicolor flow cytometry. In gastric cancer tissue, the percentage of Tregs among the CD4+ T cell subset was substantially increased compared to that of Tregs among peripheral blood CD4+ T cells from the controls. High frequency of CD8+ T cells among CD3+ T cells correlated with increased overall survival (OS) ( p = 0.005). High frequency of Tregs among CD4+ T cells correlated with increased OS ( p < 0.001), and disease-free survival (DFS) ( p = 0.039) and was an independent prognostic factor in OS (Hazard ratio: 0.047; 95% confidence interval, 0.006–0.372; p = 0.004). High frequency of MDSCs among total examined cells correlated with decreased OS ( p = 0.027) and was an independent prognostic factor in OS (Hazard ratio 8.601; 95% confidence interval, 1.240−59.678; p = 0.029). We have demonstrated that high levels of Tregs among tumor-infiltrating CD4+ T cells were favorable, but an increased proportion of MDSCs was an adverse independent prognostic factor in gastric cancer. Our results may provide important insights for future immunotherapy in gastric cancer.