Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Immunopharmacol Immunotoxicol. 2012 Jun;34(3):465-9. doi: 10.3109/08923973.2011.625034. Epub 2011 Oct 15.
One scenario by which tumors escape immune recognition is the constitutive activation of signal transducer and activator of transcription 3 (STAT3). This transcription factor mediates the production of tumor-derived factors that negatively influence target immune cells, such as dendritic cells, and polarize them toward immune-tolerance also through the induction of STAT3 activation. In the current study, the effect of p-STAT3-positive murine colon carcinoma cell line (CT26) on bone marrow-derived DCs was examined. The results showed a remarkable increase in p-STAT3 in dendritic cells (DCs) only after CT26-CM incubation. The induction of p-STAT3 in CT26-CM exposed DCs was attributed at least in part to the high levels of interleukin-6 secreted by CT26 in culture. This was also accompanied by a significant reduction in the response to the immunostimulatory adjuvant lipopolysaccharide by lowering the expression of co-stimulatory molecules CD86 and CD40. Taken together, the results suggest an inhibitory effect of CT26 colon carcinoma on DC maturation through induction of STAT3 phosphorylation. Therefore, tumor-induced p-STAT3 in DCs can be seen as a promising target for colon cancer immunotherapy.
肿瘤逃避免疫识别的一种情况是信号转导子和转录激活子 3（STAT3）的组成性激活。这种转录因子介导肿瘤衍生因子的产生，这些因子通过诱导 STAT3 激活对靶免疫细胞（如树突状细胞）产生负面影响，并使它们向免疫耐受方向极化。在本研究中，研究了 p-STAT3 阳性鼠结肠癌细胞系（CT26）对骨髓来源的树突状细胞（DC）的影响。结果表明，只有在 CT26-CM 孵育后，树突状细胞（DC）中的 p-STAT3 才会显著增加。CT26-CM 暴露的 DC 中 p-STAT3 的诱导至少部分归因于 CT26 在培养中分泌的高水平白细胞介素-6。这也伴随着共刺激分子 CD86 和 CD40 的表达降低，对免疫刺激性佐剂脂多糖的反应显著降低。综上所述，结果表明 CT26 结肠癌细胞通过诱导 STAT3 磷酸化对 DC 成熟具有抑制作用。因此，肿瘤诱导的 DC 中的 p-STAT3 可被视为结肠癌免疫治疗的一个有前途的靶点。
