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廖旺军团队牵头开发肿瘤微环境评价方法,可精准筛选胃癌免疫治疗获益人群

时间:2021-08-16 21:26:12  来源:   编辑:张淼  作者:  点击:

近日,由南方医院廖旺军团队牵头,与韩国三星医院及广东省多家医院合作(中山大学肿瘤防治中心,广东省中医院,中山大学第六附属医院,中山大学第一附属医院),系统验证了前期开发的肿瘤微环境评分体系(TMEscore)对胃癌免疫治疗反应精准预测能力,相关研究成果发表于国际癌症免疫治疗学会(SITC)官方期刊《Journal for ImmunoTherapy of Cancer》(IF 13.751)(1)。

2019年,廖旺军团队基于1524名胃癌患者的肿瘤微环境数据,运用无监督聚类和共识聚类算法发现胃癌患者存在三类稳定的肿瘤微环境分型。该分型不仅可有效区分不同微环境特性的胃癌患者,由该分型延伸出的微环境评分TMEscore可精准量化包括胃癌在内多种实体瘤组织的免疫激活状态,进而预测肿瘤患者对免疫治疗的疗效。该研究于2019年发表于Cancer Immunology Research,IF = 11.151,2020年获评ESI高被引论文(被引157次),2021年入选AACR最佳研究(全球共42个/年)。

为进一步推进肿瘤微环境评价体系的临床转化,研究团队与韩国三星医院建立合作,系统验证了TMEscore预测晚期转移性胃癌患者免疫治疗的疗效(前瞻性2期临床试验,NCT02589496),进一步,研究团队开发了NanoString检测试剂盒并联合广东省多个医院,收集检测了48例晚期胃癌免疫治疗单药或联合治疗前的标本,数据显示TMEscore的预测准确性显著优于CPS(PD-L1), MSI, TMB, EBV和GEP等基因评分。

利用胃癌的生物多组学数据,研究团队还发现ARID1APIK3CA基因突变与胃癌肿瘤微环境评分显著正相关,并鉴定了多个与肿瘤微环境激活相关的突变位点。

基于前期研究成果,廖旺军教授团队正在开展一项晚期胃癌前瞻性的临床观察性研究(NCT04850716)和一项胃癌围手术期免疫治疗与肿瘤微环境的观察性研究(NCT04850729),前瞻性验证肿瘤微环境评分对于胃癌免疫治疗的临床价值。

近年,廖旺军团队围绕肿瘤的肿瘤微环境评价,演进和改造开展了系列研究工作(1-10)。包括开发系统的肿瘤微环境评价方法以建立肿瘤的精准治疗决策体系,探索肿瘤免疫治疗耐药机制以优化治疗策略,研发新型纳米载药材料以改造肿瘤微环境和提高临床治疗疗效。相关研究成果发表于ACS Nano,Journal for ImmunoTherapy of CancerCancer Immunology ResearchOncogeneAdv Funct MaterialsTheranosticsBritish Journal of SurgeryEbioMedicineJAMA Network Open和Frontiers in Immunology等杂志。

引文

1.D. Zenget al., Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer.Journal for ImmunoTherapy of Cancer9, (2021).

2.D. Zenget al., Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures.Cancer Immunology Research7, 737-750 (2019).

3.D. Zenget al., IOBR: Multi-Omics Immuno-Oncology Biological Research to Decode Tumor Microenvironment and Signatures.Frontiers in Immunology12, 2547 (2021).

4.D. Zenget al., Gene expression profiles for a prognostic immunoscore in gastric cancer.BJS (British Journal of Surgery)105, 1338-1348 (2018).

5.S. Linet al., A novel assessing system for predicting the prognosis of gastric cancer.Epigenomics11, 1251-1266 (2019).

6.Y. Yuet al., Association of Survival and Immune-Related Biomarkers With Immunotherapy in Patients With Non-Small Cell Lung Cancer: A Meta-analysis and Individual Patient-Level Analysis.JAMA Netw Open2, e196879 (2019).

7.R. Zhouet al., A robust panel based on tumour microenvironment genes for prognostic prediction and tailoring therapies in stage I-III colon cancer.EBioMedicine42, 420-430 (2019).

8.D. Zenget al., Macrophage correlates with immunophenotype and predicts anti-PD-L1 response of urothelial cancer.Theranostics10, 7002-7014 (2020).

9.Y. Fanget al., Comprehensive analyses reveal TKI-induced remodeling of the tumor immune microenvironment in EGFR/ALK-positive non-small-cell lung cancer.OncoImmunology10, (2021).

10.H. Sunet al., CRIP1 cooperates with BRCA2 to drive the nuclear enrichment of RAD51 and to facilitate homologous repair upon DNA damage induced by chemotherapy.Oncogene, (2021).

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