Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
PLoS One. 2012;7(6):e38783. doi: 10.1371/journal.pone.0038783. Epub 2012 Jun 28.
NY-ESO-1 cancer testis (CT) antigen is an attractive candidate for immunotherapy as a result of its high immunogenicity. The aim of this study was to explore the potential for NY-ESO-1 antigen directed immunotherapy in triple negative breast cancer (TNBC) by determining the frequency of expression by immunohistochemistry (IHC) and the degree of inherent immunogenicity to NY-ESO-1.
168 TNBC and 47 ER+/HER2- primary breast cancer specimens were used to determine NY-ESO-1 frequency by IHC. As previous studies have shown that patients with a robust innate humoral immune response to CT antigens are more likely to develop CD8 T-cell responses to NY-ESO-1 peptides, we evaluated the degree to which patients with NY-ESO-1 expression had inherent immunogenicity by measuring antibodies. The relationship between NY-ESO-1 expression and CD8+ T lymphocytes was also examined.
The frequency of NY-ESO-1 expression in the TNBC cohort was 16% versus 2% in ER+/HER2- patients. A higher NY-ESO-1 score was associated with a younger age at diagnosis in the TNBC patients with NY-ESO-1 expression (p = 0.026). No differences in OS (p = 0.278) or PFS (p = 0.238) by NY-ESO-1 expression status were detected. Antibody responses to NY-ESO-1 were found in 73% of TNBC patients whose tumors were NY-ESO-1 positive. NY-ESO-1 positive patients had higher CD8 counts than negative patients (p = 0.018).
NY-ESO-1 is expressed in a substantial subset of TNBC patients and leads to a high humoral immune response in a large proportion of these individuals. Given these observations, patients with TNBC may benefit from targeted therapies directed against NY-ESO-1.
NY-ESO-1 癌症睾丸抗原(CT)由于其高度的免疫原性,是免疫治疗的一个有吸引力的候选物。本研究旨在通过免疫组化(IHC)确定其表达频率和对 NY-ESO-1 的固有免疫原性程度,来探索 NY-ESO-1 抗原导向免疫疗法在三阴性乳腺癌(TNBC)中的潜力。
使用 168 例 TNBC 和 47 例 ER+/HER2-原发性乳腺癌标本通过 IHC 确定 NY-ESO-1 的表达频率。由于先前的研究表明,对 CT 抗原具有强大固有体液免疫反应的患者更有可能对 NY-ESO-1 肽产生 CD8 T 细胞反应,因此我们通过测量抗体来评估具有 NY-ESO-1 表达的患者的固有免疫原性程度。还检查了 NY-ESO-1 表达与 CD8+T 淋巴细胞之间的关系。
在 TNBC 队列中,NY-ESO-1 的表达频率为 16%,而在 ER+/HER2-患者中为 2%。在具有 NY-ESO-1 表达的 TNBC 患者中,NY-ESO-1 评分较高与诊断时年龄较小相关(p = 0.026)。根据 NY-ESO-1 表达状态,未发现 OS(p = 0.278)或 PFS(p = 0.238)差异。在 NY-ESO-1 阳性的 TNBC 患者中发现了针对 NY-ESO-1 的抗体反应,占 73%。NY-ESO-1 阳性患者的 CD8 计数高于阴性患者(p = 0.018)。
NY-ESO-1 在相当一部分 TNBC 患者中表达,并导致其中很大一部分患者产生高体液免疫反应。鉴于这些观察结果,TNBC 患者可能受益于针对 NY-ESO-1 的靶向治疗。