Choi Han Sol, Ha Sang Yun, Kim Hye-Mi, Ahn Soo Min, Kang Myung-Soo, Kim Kyoung-Mee, Choi Min Gew, Lee Joon Ho, Sohn Tae Sung, Bae Jae Moon, Kim Sung, Kang Eun-Suk
Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oncotarget. 2016 Feb 16;7(7):7940-51. doi: 10.18632/oncotarget.6958.
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.
肿瘤浸润淋巴细胞（TILs），尤其是调节性T细胞（Tregs）和髓源性抑制细胞（MDSCs）在胃癌中的预后影响尚无定论。我们通过多色流式细胞术研究了28例胃癌组织中TILs的频率，包括CD8 + T细胞、CD45 + CD4 + CD25±FOXP3 + Tregs、CD45 + CD11b + CD14 + HLA-DR - MDSCs。在胃癌组织中，与对照组外周血CD4 + T细胞中的Tregs相比，CD4 + T细胞亚群中Tregs的百分比显著增加。CD3 + T细胞中CD8 + T细胞的高频率与总生存期（OS）增加相关（p = 0.005）。CD4 + T细胞中Tregs的高频率与OS增加相关（p < 0.001）和无病生存期（DFS）（p = 0.039），并且是OS的独立预后因素（风险比：0.047；95%置信区间，0.006 - 0.372；p = 0.004）。总检测细胞中MDSCs的高频率与OS降低相关（p = 0.027），并且是OS的独立预后因素（风险比8.601；95%置信区间，1.240 - 59.678；p = 0.029）。我们已经证明，肿瘤浸润性CD4 + T细胞中高水平的Tregs是有利的，但MDSCs比例增加是胃癌中不良的独立预后因素。我们的结果可能为未来胃癌的免疫治疗提供重要见解。
