Raza Afsheen, Merhi Maysaloun, Inchakalody Varghese Philipose, Krishnankutty Roopesh, Relecom Allan, Uddin Shahab, Dermime Said
National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar.
Translational Cancer Research Facility and Clinical Trial Unit, Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar.
J Transl Med. 2020 Mar 27;18(1):140. doi: 10.1186/s12967-020-02306-y.
Cancer Immunotherapy has recently emerged as a promising and effective modality to treat different malignancies. Antigenic profiling of cancer tissues and determination of any pre-existing immune responses to cancer antigens may help predict responses to immune intervention in cancer. NY-ESO-1, a cancer testis antigen is the most immunogenic antigen to date. The promise of NY-ESO-1 as a candidate for specific immune recognition of cancer comes from its restricted expression in normal adult tissue but frequent occurrence in multiple tumors including melanoma and carcinomas of lung, esophageal, liver, gastric, prostrate, ovarian, and bladder.
This review summarizes current knowledge of NY-ESO-1 as efficient biomarker and target of immunotherapy. It also addresses limitations and challenges preventing a robust immune response to NY-ESO-1 expressing cancers, and describes pre-clinical and clinical observations relevant to NY-ESO-1 immunity, holding potential therapeutic relevance for cancer treatment.
NY-ESO-1 induces strong immune responses in cancer patients but has limited objective clinical responses to NY-ESO-1 expressing tumors due to effect of competitive negative signaling from immune-checkpoints and immune-suppressive tumor microenvironment. We propose that combination therapy to increase the efficacy of NY-ESO-1 specific immunotherapeutic interventions should be explored to unleash the immune response against NY-ESO-1 expressing tumors.
癌症免疫疗法最近已成为一种有前景且有效的治疗不同恶性肿瘤的方法。对癌组织进行抗原分析以及确定对癌症抗原预先存在的免疫反应,可能有助于预测癌症免疫干预的反应。NY-ESO-1是一种癌胚抗原,是迄今为止免疫原性最强的抗原。NY-ESO-1作为癌症特异性免疫识别候选物的前景,源于其在正常成人组织中表达受限,但在包括黑色素瘤以及肺癌、食管癌、肝癌、胃癌、前列腺癌、卵巢癌和膀胱癌在内的多种肿瘤中频繁出现。
本综述总结了目前关于NY-ESO-1作为有效生物标志物和免疫治疗靶点的知识。它还探讨了阻碍对表达NY-ESO-1的癌症产生强大免疫反应的局限性和挑战,并描述了与NY-ESO-1免疫相关的临床前和临床观察结果,这些结果对癌症治疗具有潜在的治疗意义。
NY-ESO-1在癌症患者中可诱导强烈的免疫反应,但由于免疫检查点的竞争性负信号和免疫抑制性肿瘤微环境的影响,对表达NY-ESO-1的肿瘤的客观临床反应有限。我们建议应探索联合疗法以提高NY-ESO-1特异性免疫治疗干预的疗效,从而释放针对表达NY-ESO-1的肿瘤的免疫反应。