[摘 要] 目的：观察帕博利珠单抗联合白蛋白结合型紫杉醇及奈达铂一线治疗晚期食管鳞状细胞癌（ESCC）的临床疗效及安全性。方法：收集2020年3月至2021年9月长海医院收治的晚期ESCC且有可评价病灶的患者35例，一线给予帕博利珠单抗联合白蛋白结合型紫杉醇及奈达铂治疗，用药方案为：第1天，帕博利珠单抗200 mg、白蛋白结合型紫杉醇130 mg/m2、奈达铂70 mg/m2；第8天，白蛋白结合型紫杉醇130 mg/m2；每3周重复1次。采用实体瘤客观疗效评价RECIST1.1标准评估疗效，按NCI-CTC5.0标准评估治疗过程中产生的不良反应。结果：全部35例患者均可评价疗效，其中完全缓解（CR）4例（11.4%）、部分缓解（PR）21例（60.0%）、疾病稳定（SD）10例（28.6%）、疾病进展（PD）0例，客观有效率（ORR）为71.4%，疾病控制率（DCR）为100%，中位无进展生存期（PFS）为13.4个月。最常见不良反应包括骨髓抑制、甲状腺功能异常、皮疹、发热、关节、肌肉酸痛及脱发，仅有3例（8.6%）患者发生Ⅲ级以上不良反应。结论：帕博利珠单抗联合白蛋白结合型紫杉醇及奈达铂一线治疗本组晚期ESCC的疗效较好，不良反应患者可耐受，有待进一步扩大样本进行随机对照临床研究验证。

[Abstract] Objective: To investigate the effect of IL-27 in combination with IL-15 on the anti-tumor effects of NK92 cells and the possible molecular and signaling mechanisms. Methods: NK92 cells with high IL-15 expression (IL-15-NK92 cells) were cultured in different mass concentrations of IL-27 (0, 10, 20, 30 and 60 ng/ml) for 24 h. The effects of IL-27 on IL-15 secretion, migration and proliferation of IL-15-NK92 cells were detected by ELISA, Transwell and CCK-8 assay, respectively. Flow cytometry was used to detect the expression levels of IL-15-NK92 cell surface receptors NKG2D, NKp30 and NKp46, as well as the secretion levels of perforin and granzyme B. LDH method was used to detect the cytotoxic effect of IL-15-NK92 cells on hematologic tumor cells and solid tumor cells, and WB was used to detect the expressions and phosphorylation level of STATs pathway-related proteins. Results: IL-27 at the concentration of 30 ng/ml promoted IL-15-NK92 cells secreting IL-15 (P<0.01), significantly enhanced the cell migration (P<0.05) but inhibited the proliferation of IL-15-NK92 cells (P<0.05). 30 ng/ml IL-27 could significantly promote the expressions of NKG2D, NKp30 and NKp46 on surface of IL-15-NK 92 cells, as well as elevate the secretion of perforin (all P<0.05), but didn’t affect the secretion of granzyme B (P>0.05); moreover, it also significantly enhanced the cytotoxicity of IL-15-NK92 cells against hematologic malignancies and solid tumor cells (P<0.05 or P<0.01), and up-regulated the phosphorylation levels of STAT1, STAT3 and STAT5 (all P<0.01). Conclusion: IL-27 can enhance the cytotoxicity of IL-15-NK92 cells against hematologic tumor cells and solid tumor cells, which might be related with its upregulation of phosphorylation level of STAT1, STAT3 and STAT5 in JAK-STAT pathway and multiple activating receptors in IL-15-NK92 cells.