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目的探讨肿瘤相关巨噬细胞(TAMs)的信号转导和激活子3(STAT3)信号途径在抗乳腺癌免疫应答中的作用。方法用大鼠乳腺癌细胞的培养上清液诱导培养大鼠的腹腔巨噬细胞,再用STAT3诱骗寡核苷酸(decoy ODNs)抑制其STAT3的活性并用细菌的脂多糖将其激活,检测其对肿瘤细胞的杀伤活性和抗原呈递能力;将乳腺癌细胞移植到SD大鼠,然后接受诱导的巨噬细胞或转染STAT3 decoy ODNs的诱导巨噬细胞的处理,检测肿瘤的生长和大鼠的免疫反应强度。结果伴随STAT3的过度激活,诱导的巨噬细胞对肿瘤细胞的细胞毒性和抗原呈递能力减弱。 STAT3 decoy ODNs增强诱导的巨噬细胞的杀伤活性,与对照组比较,差异有统计学意义(P< 0．01);增强诱导的巨噬细胞的抗原呈递能力,巨噬细胞呈递抗原刺激的淋巴细胞的增殖能力、IFN- γ产量及细胞毒性与对照组比较,差异有统计学意义(P值均<0．01)。STAT3活性被抑制的巨噬细胞能增强大鼠对移植乳腺癌的免疫反应而抑制肿瘤的生长,在第24、28、32天,STAT3 decoy ODNs 处理组的肿瘤体积与其他各组比较,差异有统计学意义(P值均<0．01)。结论 TAMs的免疫抑制作用可能与其STAT3信号过度激活有关,抑制其STAT3信号能增强机体对乳腺癌的免疫应答反应。
Objective To investigate the role of signal transducer and activator of transcription 3 (STAT3) signaling pathways in tumor-associated macrophages (TAMs) in the anti-breast cancer immune response. Methods Rat peritoneal macrophages were induced by culture supernatant of rat breast cancer cells, and then STAT3 activity was inhibited by STAT3 decoy ODNs and activated by bacterial lipopolysaccharide Tumor cell killing activity and antigen presenting ability; Breast cancer cells were transplanted into SD rats and then treated with induced macrophages or induced macrophages transfected with STAT3 decoy ODNs to detect tumor growth and rat Intensity of immune reaction. Results With the over-activation of STAT3, the induced macrophages decreased the cytotoxicity and antigen-presenting ability of tumor cells. STAT3 decoy ODNs enhanced the cytotoxic activity of macrophages, compared with the control group, the difference was statistically significant (P <0.01); enhanced antigen-presenting ability of macrophages, macrophages presented antigen-stimulated lymph Cell proliferation, IFN-γ production and cytotoxicity compared with the control group, the difference was statistically significant (P all <0.01). The macrophages whose STAT3 activity was inhibited could enhance the immune response and inhibit the tumor growth in rats, and the tumor volume of STAT3 decoy ODNs treated groups on the 24th, 28th and 32nd days were significantly different from other groups Statistical significance (P <0.01). Conclusions The immunosuppressive effects of TAMs may be related to the over-activation of STAT3 signaling. Inhibition of STAT3 signaling can enhance the immune response to breast cancer.