Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands.
Br J Cancer. 2010 Oct 26;103(9):1415-21. doi: 10.1038/sj.bjc.6605935. Epub 2010 Oct 5.
Dendritic cell (DC) vaccination has been shown to induce anti-tumour immune responses in cancer patients, but so far its clinical efficacy is limited. Recent evidence supports an immunogenic effect of cytotoxic chemotherapy. Pre-clinical data indicate that the combination of chemotherapy and immunotherapy may result in an enhanced anti-cancer activity. Most studies have focused on the immunogenic aspect of chemotherapy-induced cell death, but only few studies have investigated the effect of chemotherapeutic agents on the effector lymphocytes of the immune system.
Here we investigated the effect of treatment with oxaliplatin and capecitabine on non-specific and specific DC vaccine-induced adaptive immune responses. Stage III colon cancer patients receiving standard adjuvant oxaliplatin/capecitabine chemotherapy were vaccinated at the same time with keyhole limpet haemocyanin (KLH) and carcinoembryonic antigen (CEA)-peptide pulsed DCs.
In 4 out of 7 patients, functional CEA-specific T-cell responses were found at delayed type hypersensitivity (DTH) skin testing. In addition, we observed an enhanced non-specific T-cell reactivity upon oxaliplatin administration. KLH-specific T-cell responses remained unaffected by the chemotherapy, whereas B-cell responses were diminished.
The results strongly support further testing of the combined use of specific anti-tumour vaccination with oxaliplatin-based chemotherapy.
树突状细胞 (DC) 疫苗接种已被证明可在癌症患者中诱导抗肿瘤免疫反应,但迄今为止其临床疗效有限。最近的证据支持细胞毒性化疗具有免疫原性作用。临床前数据表明,化疗和免疫疗法的联合使用可能会增强抗癌活性。大多数研究都集中在化疗诱导的细胞死亡的免疫原性方面,但只有少数研究调查了化疗药物对免疫系统效应淋巴细胞的影响。
在这里,我们研究了奥沙利铂和卡培他滨治疗对非特异性和特异性 DC 疫苗诱导的适应性免疫反应的影响。接受标准辅助奥沙利铂/卡培他滨化疗的 III 期结肠癌患者同时接受钥孔血蓝蛋白 (KLH) 和癌胚抗原 (CEA)-肽脉冲 DC 疫苗接种。
在 7 名患者中的 4 名中,在迟发型超敏反应 (DTH) 皮肤试验中发现了功能性 CEA 特异性 T 细胞反应。此外,我们观察到奥沙利铂给药后非特异性 T 细胞反应增强。KLH 特异性 T 细胞反应不受化疗影响,而 B 细胞反应减弱。
这些结果强烈支持进一步测试特异性抗肿瘤疫苗接种与基于奥沙利铂的化疗联合使用。