胃肠道间质肿瘤:微环境特点及免疫治疗思路

Gastrointestinal stromal tumor:immune microenvironment characteristics and immunotherapy ideas

胃肠道间质肿瘤(GIST)是胃肠道最常见的间充质来源的肿瘤,对放化疗敏感性低。近二十年来,以伊马替尼为代表的酪氨酸激酶抑制剂类药物在很大程度上改善了GIST患者的预后,但仍有相当数量的患者出现原发或继发性耐药,因此需要开拓新的治疗方法。随着肿瘤免疫治疗的基础与临床研究的进展,越来越多的肿瘤患者从免疫治疗中获益。但是,免疫治疗在GIST中的应用却较为缓慢。目前,免疫检查点抑制剂治疗在GIST中的应用取得了初步进展,未来还需要有更多的循证证据。在发展迅速的免疫细胞疗法和肿瘤疫苗领域,目前尚无相关新技术用于GIST的临床研究。尽管如此,GIST的免疫微环境具有丰富的免疫细胞浸润,提示GIST是潜在的免疫治疗优势病种。但是,免疫治疗在GIST中的应用不能“照搬”上皮来源肿瘤的特征,必须在充分了解GIST免疫特征的基础上,进行针对性研究,开发出基于GIST的免疫治疗策略,才能使免疫治疗真正改善患者的预后。

Gastrointestinal stromal tumor(GIST)is the most common mesenchymal tumor in the gastrointestinal tract,which is insensitive to radiotherapy or chemotherapy.In the past two decades,the tyrosine kinase inhibitors(e.g.imatinib)have greatly improved the prognosis of patients with GIST,but primary or secondary drug resistance occurred in a considerable number of patients.Therefore,it is necessary to explore new treatments.With the development of basic and clinical researches in tumor immunotherapies,more and more patients with various tumors have benefited from immunotherapy.However,the application of immunotherapy in the treatment of GIST progressed rather slowly.Although there is some progress in immune checkpoint therapy for GIST,more evidence is required in the future.In the promising fields of immune cell therapy and neoantigen vaccine,no new technology has been introduced into the clinical studies of GIST.Nevertheless,GIST has abundant immune cell infiltration in immune microenvironment,suggesting that GIST may benefit from immunotherapy.Instead of directly using the characteristics of epithelium-derived tumors,immunotherapy studies in GIST should be based on thorough understanding of the unique immune signature of GIST.Only through targeted researches and GIST-specific immunotherapy,could immunotherapy of GIST truly improve the prognosis of patients with GIST.