Agarwal Sumit, Saini Shikha, Parashar Deepak, Verma Archana, Sinha Abhilasha, Jagadish Nirmala, Batra Aruna, Suri Sushma, Gupta Anju, Ansari Abdul S, Lohiya Nirmal Kumar, Suri Anil
Cancer Microarray; Genes and Proteins Laboratory; National Institute of Immunology; Aruna Asaf Ali Marg; New Delhi, India.
Oncoimmunology. 2013 May 1;2(5):e24270. doi: 10.4161/onci.24270. Epub 2013 Apr 1.
Ovarian cancer is one of the neoplasms affecting the reproductive tract associated with high mortality rate because of limited therapeutic options and an elevated incidence of chemoresistance and recurrence. In this context, immunotherapy may constitute a promising approach to improve survival rates and clinical outcome, raising the need for specific target antigens. Cancer-testis antigens (CTAs) are considered promising candidates in this sense because they are aberrant expressed by various malignancies but not by non-transformed tissue, with the exception of testes. Here, we examined the expression and potential to promote humoral immune responses of a novel CTA, A-kinase anchor protein 4 (AKAP4), among 38 ovarian carcinoma patients. Our results reveal that AKAP4 was expressed at both the mRNA and protein levels in 89% (34/38) of ovarian carcinoma tissue specimens but not in 21 matched adjacent non-cancerous tissues. In addition, a humoral response against AKAP4 was detected in 58% (22/38) of ovarian carcinoma patients by ELISA. In particular, 65% (22/34) patients bearing an AKAP4-expressing tumor exhibited circulating anti-AKAP4 antibodies. Interestingly, the majority of specimens were categorized as ovarian serous adenocarcinoma and serous papillary carcinoma, of which 93% (28/30) and 100% (6/6), respectively, expressed AKAP4. A humoral response against AKAP4 was detected in 79% (19/24) and 67% (4/6) of ovarian serous adenocarcinoma and serous papillary carcinoma patients, respectively. The presence of circulating anti-AKAP4 antibodies suggests the AKAP4 is highly immunogenic in ovarian serous carcinoma patients. Our study lays the foundations for exploring AKAP4 as a potential target for the immunotherapy of ovarian cancer.
卵巢癌是影响生殖道的肿瘤之一,由于治疗选择有限以及化疗耐药和复发率升高,其死亡率很高。在这种情况下,免疫疗法可能是提高生存率和临床结果的一种有前景的方法,这就增加了对特定靶抗原的需求。从这个意义上讲,癌-睾丸抗原(CTA)被认为是有前景的候选者,因为它们在各种恶性肿瘤中异常表达,但在非转化组织中(睾丸除外)不表达。在这里,我们检测了一种新型CTA,即A激酶锚定蛋白4(AKAP4)在38例卵巢癌患者中的表达及其促进体液免疫反应的潜力。我们的结果显示,89%(34/38)的卵巢癌组织标本中AKAP4在mRNA和蛋白水平均有表达,但在21例匹配的相邻非癌组织中未表达。此外,通过酶联免疫吸附测定(ELISA)在58%(22/38)的卵巢癌患者中检测到针对AKAP4的体液反应。特别是,65%(22/34)携带表达AKAP4肿瘤的患者出现循环抗AKAP4抗体。有趣的是,大多数标本被归类为卵巢浆液性腺癌和浆液性乳头状癌,其中分别有93%(28/30)和100%(6/6)表达AKAP4。在卵巢浆液性腺癌和浆液性乳头状癌患者中,分别有79%(19/24)和67%(4/6)检测到针对AKAP4的体液反应。循环抗AKAP4抗体的存在表明AKAP4在卵巢浆液性癌患者中具有高度免疫原性。我们的研究为探索将AKAP4作为卵巢癌免疫治疗的潜在靶点奠定了基础。