Detection of IgG antibody reactive to a p53-derived peptide with HLA-A4601 binding motif in breast cancer patients

目的：我们先前报道在乳腺癌患者中存在P53衍生的非突变多肽作为细胞毒性T淋巴细胞(CTL)表位(参考文献11)。我们还证明对CTL表位多肽的抗体反应可作为预测癌症患者接受多肽疫苗接种的预后的实验室标志物(参考文献14)。本研究的目的是为了更好地了解BC患者对P53多肽的免疫应答。实验设计：检测104例BC患者、50例前列腺癌患者(PC)、50例自身免疫性疾病患者(AI)、24例特应性疾病患者(AD)和83例健康献血者(HD)血清中的抗P53多肽。结果：BC和AL患者的p53377-385特异性免疫球蛋白水平均显著高于AD、PC和HD患者。23%的BC患者、0%的PC患者、32%的AI患者、4%的AD患者和5%的HD患者的血清中检测到显著水平的p53377-385抗体。血清中抗p53377-385的活性被相应的多肽吸收而大大降低，但不能被整个P53蛋白吸收。12例(12%)BC患者血清中可检测到P53蛋白特异性抗体，其中仅4例抗P53377-385抗体阳性。在预后方面，这种抗肽抗体与预后不相关，但在分期、肿瘤细胞侵袭和复发方面似乎与预后良好有关。结论：这些结果可能为在多肽水平上更好地了解BC患者对P53抗原的免疫应答提供新的见解。

Purpose : We previously reported the existence of p53-derived non-mutated peptides as cytotoxic T lymphocyte(CTL) epitopes in breast cancer(BC) patients(Ref.11). We also demonstrated that Ab reactive to CTL epitope peptides can be used as a laboratory marker to predict better estimate the prognosis of cancer patients receiving peptide vaccinations(Ref.14). The object of this study was to better understand the immune responses to p53-peptides in BC patients. Experimental Design : We measured anti-p53-peptides in the sera of patients with BC(n=104), prostate cancer(PC, n=50), autoimmune diseases(AI, n=50), atopic disease(AD, n=24), and healthy donors(HDs, n=83). Result : The levels of IgG specific to the p53377-385 in both BC and Al patients were significantly higher than those in AD, PC, and HDs. Significant levels of the anti-p53377-385 IgG were detected in the sera from 23% of the patients with BC, 0% with PC, 32% with AI, 4% with AD, and 5% HDs. Anti-p53377-385 activity in the sera was largely reduced by absorption with the corresponding peptide, but not with the entire p53-protein. IgG reactive to entire p53-protein was detectable in the sera from 12 BC patients(12%), and only 4 of those patients were positive for anti-p53377-385 IgG. As regards prognosis, this anti-peptide Ab did not correlate with a poor prognosis, but rather seemed to be associated with a good prognosis of these BC patients in terms of stage, invasion of tumor cells, and recurrence. Conclusions : These results may provide new insight to achieve a better understanding of the immune responses to p53 antigen at the peptide level in BC patients.