Da Gama Duarte Jessica, Woods Katherine, Quigley Luke T, Deceneux Cyril, Tutuka Candani, Witkowski Tom, Ostrouska Simone, Hudson Chris, Tsao Simon Chang-Hao, Pasam Anupama, Dobrovic Alexander, Blackburn Jonathan M, Cebon Jonathan, Behren Andreas
Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia.
School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia.
Cancers (Basel). 2021 Apr 9;13(8):1805. doi: 10.3390/cancers13081805.
Antibodies that block immune regulatory checkpoints (programmed cell death 1, PD-1 and cytotoxic T-lymphocyte-associated antigen 4, CTLA-4) to mobilise immunity have shown unprecedented clinical efficacy against cancer, demonstrating the importance of antigen-specific tumour recognition. Despite this, many patients still fail to benefit from these treatments and additional approaches are being sought. These include mechanisms that boost antigen-specific immunity either by vaccination or adoptive transfer of effector cells. Other than neoantigens, epigenetically regulated and shared antigens such as NY-ESO-1 are attractive targets; however, tissue expression is often heterogeneous and weak. Therefore, peptide-specific therapies combining multiple antigens rationally selected to give additive anti-cancer benefits are necessary to achieve optimal outcomes. Here, we show that Ropporin-1 (ROPN1) and 1B (ROPN1B), cancer restricted antigens, are highly expressed and immunogenic, inducing humoral immunity in patients with advanced metastatic melanoma. By multispectral immunohistochemistry, 88.5% of melanoma patients tested ( = 54/61) showed ROPN1B expression in at least 1 of 2/3 tumour cores in tissue microarrays. Antibody responses against ROPN1A and ROPN1B were detected in 71.2% of melanoma patients tested ( = 74/104), with increased reactivity seen with more advanced disease stages. Thus, ROPN1A and ROPN1B may indeed be viable targets for cancer immunotherapy, alone or in combination with other cancer antigens, and could be combined with additional therapies such as immune checkpoint blockade.
阻断免疫调节检查点（程序性细胞死亡蛋白1，PD - 1和细胞毒性T淋巴细胞相关抗原4，CTLA - 4）以调动免疫力的抗体已显示出对癌症前所未有的临床疗效，证明了抗原特异性肿瘤识别的重要性。尽管如此，许多患者仍无法从这些治疗中获益，因此正在寻求其他方法。这些方法包括通过疫苗接种或效应细胞的过继转移来增强抗原特异性免疫的机制。除了新抗原外，表观遗传调控的共享抗原如NY - ESO - 1是有吸引力的靶点；然而，组织表达通常是异质性的且较弱。因此，为了实现最佳疗效，需要将合理选择的多种抗原结合起来的肽特异性疗法以产生累加的抗癌益处。在这里，我们表明，癌症限制性抗原Ropporin - 1（ROPN1）和1B（ROPN1B）高度表达且具有免疫原性，可在晚期转移性黑色素瘤患者中诱导体液免疫。通过多光谱免疫组织化学，在检测的黑色素瘤患者中（n = 54/61），88.5%在组织微阵列的2/3个肿瘤核心中的至少1个中显示出ROPN1B表达。在检测的黑色素瘤患者中（n = 74/104），71.2%检测到针对ROPN1A和ROPN1B的抗体反应，随着疾病阶段的进展反应性增加。因此，ROPN1A和ROPN1B确实可能是癌症免疫治疗的可行靶点，单独或与其他癌症抗原联合使用，并可与免疫检查点阻断等其他疗法联合使用。
