Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany,
Cancer Immunol Immunother. 2014 Jan;63(1):59-65. doi: 10.1007/s00262-013-1485-8. Epub 2013 Oct 16.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human neoplasms, having extremely poor prognosis with a 5-year survival rate of <1 % and a median survival of 6 months. In contrast to other malignancies, pancreatic cancer is highly resistant to chemotherapy and targeted therapy. Therefore, new treatment options are urgently needed to improve the survival of patients with PDAC. Based on our data showing that patients with higher CD8+ T cell tumour infiltration exhibited prolonged overall and disease-free survival compared to patients with lower or without CD8+ T cell tumour infiltration, we suggested that immunotherapy could be a promising treatment option for PDAC. However, clinical data from the chemoradioimmunotherapy with interferon-α (IFN) trial did not point to an improved efficiency of chemoradiation combined with IFN as compared to chemoradiotherapy alone, suggesting an important role of the immune suppression induced by PDAC and/or unspecific immune stimulation. In support of this hypothesis, we found that the PDAC patients and experimental mice had an increased number of regulatory T cells and myeloid-derived suppressor cells. These results allowed us to conclude that PDAC provokes not only an anti-tumour immune response, but also strong immune suppression. Thus, we supposed that new immunotherapeutical strategies should involve not only stimulation of the immune system of PDAC patients, but also exert control over the tumour immune suppressive milieu.
胰腺导管腺癌 (PDAC) 是最具侵袭性的人类肿瘤之一，预后极差，5 年生存率<1%，中位生存期 6 个月。与其他恶性肿瘤不同，胰腺癌对化疗和靶向治疗具有高度耐药性。因此，迫切需要新的治疗方案来改善 PDAC 患者的生存。基于我们的数据表明，与 CD8+T 细胞肿瘤浸润较低或无 CD8+T 细胞肿瘤浸润的患者相比，CD8+T 细胞肿瘤浸润较高的患者表现出更长的总生存期和无病生存期，我们推测免疫疗法可能是 PDAC 的一种有前途的治疗选择。然而，干扰素-α (IFN) 联合放化疗的化学放射免疫治疗临床试验的临床数据并未表明与单纯放化疗相比，联合 IFN 的放化疗增效，这表明 PDAC 诱导的免疫抑制和/或非特异性免疫刺激的重要作用。支持这一假设，我们发现 PDAC 患者和实验小鼠的调节性 T 细胞和髓源性抑制细胞数量增加。这些结果使我们得出结论，PDAC 不仅引发了抗肿瘤免疫反应，而且还引发了强烈的免疫抑制。因此，我们推测新的免疫治疗策略不仅应包括刺激 PDAC 患者的免疫系统，还应控制肿瘤免疫抑制环境。
