Local radiotherapy increases the level of autoantibodies to ribosomal P0 protein but not to heat shock proteins, extracellular matrix molecules and EGFR/ErbB2 receptors in prostate cancer patients

Local radiotherapy increases the level of autoantibodies to ribosomal P0 protein but not to heat shock proteins, extracellular matrix molecules and EGFR/ErbB2 receptors in prostate cancer patients
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DOI:
10.3892/or.2012.2197
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发表时间:
2013-03-01
期刊:
影响因子:
4.2
通讯作者:
Bei, Roberto
Bei, Roberto
中科院分区:
医学3区
文献类型:
--
作者:
Ingrosso, Gianluca;Fantini, Massin;Bei, Roberto

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前列腺癌是发达国家男性中常见的癌症。虽然激素治疗和放射治疗(RT)是治疗前列腺癌的有效方法,但新的免疫方法已经被探索。使用癌症疫苗的临床试验的发展表明,对肿瘤抗原的免疫反应可以增强,接种疫苗可以提高患者的生存率。经过标准治疗后,对肿瘤抗原的免疫反应也可以增强。在本研究中,我们测定了35例前列腺癌患者在局部放疗和激素治疗前后的细胞外基质(ECM)分子、热休克蛋白(HSP)、核糖体P0蛋白、EGFR、ErbB2和前列腺特异性抗原(PSA)抗体的发生情况。我们证明了对P0, ECM分子[胶原(C) CI, CIII, CV,纤维连接蛋白(FN)和层粘连蛋白(LM)]和HSP90的免疫与未经治疗的患者的恶性肿瘤有关。所有患者血清均未出现EGFR抗体,而2例和1例患者分别对ErbB2和PSA有反应。我们还发现治疗8个月后血清中CI、CIII、FN和HSP90的IgG水平显著降低。相反,10例患者治疗后P0自身抗体水平升高。10例P0自身抗体水平升高的患者中有5例接受RT +激素治疗。治疗并未改变患者的EGFR、ErbB2和PSA抗体水平。我们的结果表明,前列腺癌患者标准治疗后抗体水平对自身分子的修饰受抗原类型的影响。核糖体P0蛋白似乎是一种高免疫原性抗原,其免疫原性在rt后增加。此外,10例P0自身抗体水平升高的患者在18个月时的PSA平均水平低于其余25例患者。本研究可能有助于更好地了解前列腺癌患者在标准治疗后的免疫生物学行为。
Prostate cancer is a common cancer among men in developed countries. Although hormonotherapy and radiotherapy (RT) represent valid therapies for prostate cancer treatment, novel immunological approaches have been explored. The development of clinical trials employing cancer vaccines has indicated that immune response to tumor antigens can be boosted and that vaccine administration can improve patient survival. Immune response to tumor antigens could also be enhanced after standard therapies. In the present study, we determined the occurrence of antibodies to extracellular matrix (ECM) molecules, heat shock protein (HSP), ribosomal P0 protein, EGFR, ErbB2 and prostate-specific antigen (PSA) in 35 prostate cancer patients prior to and following local RT and hormonotherapy. We demonstrated that immunity to P0, ECM molecules [collagens (C) CI, CIII, CV, fibronectin (FN) and laminin (LM)] and to HSP90 was associated with malignancy in untreated patients. None of the patient sera showed antibodies to EGFR, while 2 and 1 patients showed reactivity to ErbB2 and PSA, respectively. We also demonstrated that 8 months after therapy the IgG serum levels to CI, CIII, FN and HSP90 significantly decreased. Conversely, the level of P0 autoantibodies increased after therapy in 10 patients. Five of the 10 patients with increased levels of P0 autoantibodies were treated with RT plus hormonotherapy. Treatment of patients did not change the levels of antibodies against EGFR, ErbB2 and PSA. Our results indicated that the modification of antibody level to self molecules after standard treatment of prostate cancer patients is influenced by the type of antigen. Ribosomal P0 protein appears to be a high immunogenic antigen and its immunogenicity increases following RT. In addition, 10 patients with increased levels of autoantibodies to P0 showed PSA mean levels lower than the remaining 25 patients at 18 months. This study may contribute to a better understanding of the immunobiological behavior of prostate cancer patients following standard treatment.