外周血 PD-1 和 Tim-3 的百分比与腹膜肿瘤的原发部位和病理类型有关。
Peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms.
发表日期:2023 Mar 29
作者:
Huihui Hu, Jin Zhao, Judong Yuan, Man Zhang
来源:
Cellular & Molecular Immunology
摘要:
编程死亡-1(PD-1)和T细胞免疫球蛋白和粘附分子3(Tim-3)可作为腹膜肿瘤患者治疗的生物标志物。本研究探讨了外周PD-1和Tim-3的差异百分比,以研究其是否与腹膜肿瘤患者的原发部位和病理类型有关联。我们还研究了PD-1和Tim-3在循环淋巴细胞、CD3 + T细胞、CD3 + CD4 + T细胞和CD3 + CD8 + T细胞中的频率,以确定是否与腹膜肿瘤患者的无进展生存期相关。我们招募了115名腹膜肿瘤患者,并对其进行多色流式细胞术分析,以确定循环淋巴细胞、CD3 + T细胞、CD3 + CD4 + T细胞和CD3 + CD8 + T细胞中PD-1和Tim-3受体的百分比。根据肿瘤是否有原发灶并仅限于腹膜肿瘤,将腹膜肿瘤患者分为原发组和继发组。然后,根据肿瘤的病理类型(腺癌、间皮瘤和粘液瘤),对所有患者进行重新分组。继发腹膜肿瘤组被分为不同的原发部位组(结肠、胃、妇科)。本研究还招募了38名正常志愿者。通过流式细胞术方式探测以上标志物,以找到腹膜肿瘤患者与正常对照组在外周血中的差异水平。在腹膜肿瘤组中,CD4 + T淋巴细胞、CD8 + T淋巴细胞、CD45 + PD-1 + 淋巴细胞、CD3 + PD-1 + T细胞、CD3 + CD4 + PD-1 + T细胞、CD3 + CD8 + PD-1 + T细胞和CD45 + Tim-3 + 淋巴细胞的水平高于正常对照组(p值分别为0.004、0.047、0.046、0.044、0.014、0.038和0.017)。与原发腹膜肿瘤组相比,继发腹膜肿瘤组的CD45 + PD-1 + 淋巴细胞、CD3 + PD-1 + T细胞和CD3 + CD4 + PD-1 + T细胞的比例增加(p值分别为0.010、0.044和0.040),而PD-1与继发组的原发部位无关联(P > 0.05)。Tim-3在原发腹膜肿瘤组中与继发组之间没有统计学差异(p>0.05),但CD45 + Tim-3 + %淋巴细胞、CD3 + Tim-3 + %T细胞和CD3 + CD4 + Tim-3 + T细胞与不同的腹膜肿瘤继发部位相关(p <0.05)。在不同的病理类型组中,与间皮瘤组相比,腺癌组的CD45 + PD-1 + 淋巴细胞和CD3 + PD-1 + T细胞的比例较高(p = 0.048,p = 0.045)。外周血中CD45 + PD-1 + 淋巴细胞和CD3 + PD-1 + T细胞的频率与无进展生存期(PFS)相关。我们的研究揭示了外周PD-1和Tim-3百分比与腹膜肿瘤患者的原发部位和病理类型有关。这些发现可能提供重要的评估方法,以预测腹膜肿瘤患者的免疫治疗反应。©2023作者。
Programmed death-1 (PD-1) and T cell immunoglobulin and mucin-domain-containing molecule 3(Tim-3) may be used as the biomarkers for the therapy in patients with peritoneal neoplasms. In the current study, the differential percentages of peripheral PD-1 and Tim-3 are explored to investigate whether to associate with primary sites and pathological types of patients with peritoneal neoplasms or not. We also investigated the frequencies of PD-1 and Tim-3 on circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells if would correlate with the progression-free survival of peritoneal neoplasms patients.115 patients with peritoneal neoplasms were recruited, subjected to multicolor flow cytometric analyses of the percentages of PD-1 and Tim-3 receptors of circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells. The peritoneal neoplasms patients were divided into primary group and secondary group depending on whether the tumor had primary focus and limited to peritoneal tumor or not. Then all the patients were regrouped by the pathological types of neoplasms (adenocarcinoma, mesothelioma, and pseudomyxoma). The secondary peritoneal neoplasms group was divided into the different primary site groups (colon, gastric, gynecology). This study also enrolled 38 cases of normal volunteers. The above markers were explored by flow cytometer, to find the differential levels in peritoneal neoplasms patients compared with normal group in peripheral blood.Higher levels of CD4 + T lymphocytes, CD8 + T lymphocytes, CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, CD3 + CD4 + PD-1 + T cells, CD3 + CD8 + PD-1 + T cells and CD45 + Tim-3 + lymphocytes were found in peritoneal neoplasms group than normal control (the p value was respectively 0.004, 0.047, 0.046, 0.044, 0.014, 0.038 and 0.017). Compared with primary peritoneal neoplasms group, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, and CD3 + CD4 + PD-1 + T cells were increased in the secondary peritoneal neoplasms group (the p value was respectively 0.010, 0.044, and 0.040), while PD-1 did not correlate with the primary sites in secondary group (P > 0.05). Tim-3 had no statistical differences in primary peritoneal neoplasms group compared with secondary group (p > 0.05), but CD45 + Tim-3+% lymphocytes, CD3 + Tim-3+%T cells, and CD3 + CD4 + Tim-3 + T cells were associated with different secondary sites of peritoneal neoplasms (p < 0.05). In the different pathological type groups, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells presented the higher levels in adenocarcinoma group compared with mesothelioma group (p = 0.048, p = 0.045). The frequencies of CD45 + PD-1 + lymphocytes and CD3 + PD-1 + T cells in peripheral blood were associated with progression-free survival (PFS).Our work uncovers peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms. Those findings might provide important assessment to predict peritoneal neoplasms patients' immunotherapy responses.© 2023. The Author(s).