预测胃癌免疫治疗疗效的生物学指标研究进展
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v7i4.15527
Abstract
我国胃癌的发病率和死亡率在恶性肿瘤中占比较高,免疫检查点抑制剂(ICIs)的出现极大程度上改善了胃癌患者的预后,然而临床上只有少数患者能够获得长期获益。因此,有必要探索胃癌免疫治疗的有效预测性生物学指标。近年来随着分子生物学、基因组测序技术的发展和肿瘤及宿主免疫微环境的研究不断深入,相关成果繁多。本文围绕胃癌免疫治疗疗效的预测生物学指标进行综述,为精准免疫治疗提供参考。
Keywords
胃癌；免疫治疗；疗效；生物标志物
Funding
青海大学附属医院中青年科研基金(ASRF-2023-YB-12)。
Full Text
PDF - Viewed/Downloaded: 0 TimesReferences
[1] Han B,Zheng R, Zeng H, et al.Cancer incidence and mort ality in china, 2022[J]. J Natl Cancer Cent, 2024,4(1):47-53. DOI:10.1016/j.jncc.2024.01.006.
[2] KUS T,KOSE F,AKTAS G,et al.Prediction of peritoneal rec urrence in patients with gastric cancer: a multicenter study [J].J Gastrointest Cancer,2021,52(2):634-642.
[3] Topalian SL,Hodi FS,Brahmer JR,et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer[J]. N Engl J Med,2012,366(26):2443-2454.
[4] Xu JM,Jiang HP,Pan YY,et al. Sintilimab plus chemothe rapy for unresectable gastric or gastroesophageal junction ca ncer:the ORIENT-16 randomized clinical trial[J].JAMA, 2023, 330(21):2064-2074.
[5] Janjigian YY,Shitara K,Moehler M,et al.First-line nivol umab plus chemotherapy versus chemotherapy alone for advan ced gastric, gastro-oesophageal junction,and oesophageal ade nocarcinoma(CheckMate 649):a randomised,openlabel,phase 3 trial[J].Lancet,2021,398(10294):27-40.
[6] Janjigian YY,Kawazoe A,Yañez P,et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer[J].Nature,2021,600(7890):727-730.
[7] ChaoJ,Fuchs CS,Shitara K,et al.Assessment of pembroliz umab therapy for the treatment of microsatellite instability -high gastric or gastroesophageal junction cancer among pati ents in the KEYNOTE-059,KEYNOTE-061,and KEYNOTE-062 clinic al trials[J].JAMA Oncol,2021,7(6):895-902.
[8] Zeinalian M, Hashemzadeh-Chaleshtori M, Salehi R, et al. Clinical Aspects of Microsatellite Instability Testing in Colorectal Cancer[J].Adv Biomed Res,2018,7:28.
[9] Akagi K,Oki E,Taniguchi H,et al. Realworld data on micr osatellite instability status in various unresectable or metas tatic solid tumors[J]. Cancer Sci,2021,112(3):1105-1113.
[10] Muro K,Kawakami H,Kadowki S,er al. 1513MO A phase Ⅱ study of nivolumab plus low dose ipilimumab as first-line the rapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: First results of the NO LIMIT study (WJOG13320G/CA209-7W7)[J].Ann Oncol,2023,34:s852-s853.
[11] HABER J E,Partners and pathways: reparing a doublestrand break[J].Trends in Genetics,2020,16(6):259-264.
[12] 任南,吕雪洁,何陈周,等.胃癌预后全基因组关联分析[J].中国公共卫生,2023,39(2):7.
[13] Lee Y,Kim HD,Lee SY.et al.Predictive value of homolog ous recombination-related gene mutations in survival outco mes of first-line nivolumab plus chemotherapy for gastric cancer[J].Gastric Cancer (2025).https://doi.org/10.1007/s10120-025-01648-0.
[14] 娄俊,易韵.70例卵巢癌患者治疗期间外周血T淋巴细胞亚群测定的临床意义[J].实用癌症杂志,2022,37(5):780-782.
[15] Al-Shibli KI, Donnem T, Al-Saad S, et al. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer[J].Clinical cancer research: an off icial journal of the American Association for Cancer Research,2008,14(16):5220-7.
[16] 鲍千红,吕凌云,张伟群,等.过敏性鼻炎患者血清中炎症因子、免疫球蛋白及T淋巴细胞亚群水平检测及分析[J].中国卫生检验杂志,2020,30(21):2614-2616.
[17] Lowery FJ, Goff SL, Gasmi B, et al. Neoantigen-specif ic tumor-infiltrating lymphocytes in gastrointestinal cance rs:a phase 2 trial[J].Nat Med. 2025 Apr 1.
[18] Zhang N,Cao M,Duan Y,et al.Prognostic role of tumorin filtrating lymphocytes in gastric cancer: a metaanalysis and experimental validation[J].Arch Med Sci,2020,16(5):1092-1103.
[19] 彭春伟,刘广杰,余昌俊.胃癌患者血清IL-6、IL-8、TNF-α表达水平及其临床意义分析[J].中国医学前沿杂志(电子版),2019,11(07):125-129.
[20] 冯宁,尚红港.肿瘤坏死因子-α、白介素-6和白介素-8检测在胃癌中的临床价值[J].肿瘤基础与临床,2021,34(3):244-247.
[21] 王晓倩,李丹丹,王丹,等.乳腺癌4T1细胞中过表达鼠白介素-10对宿主抗肿瘤免疫应答的影响[J].山西医科大学学报,2021,52(5):559-564.
[22] 仇海乐,戎冬文,贾军梅.肿瘤坏死因子-α瘤内注射联合化疗治疗晚期非小细胞肺癌疗效观察 [J].肿瘤基础与临床,2020,33(5):404-406.
[23] 王馨焱,代虎威,刘晓玲.外周血细胞因子预测晚期胃癌抗PD-1治疗的疗效及预后[J].现代肿瘤医学,2023,31(15):2872-2878.
[24] 谢晓虹,骆玉霜.基于细胞因子构建初始不可切除或晚期胃癌患者接受热疗联合免疫及化疗的疗效预测模型[D].青海:青海大学,2024.
[25] Ray-Coquard I,Cropet C,Van Glabbeke M,et al. Lymph openia as a prognostic factor for overall survival in advanced carcinomas,sarcomas, and lymphomas[J].Cancer Res,2009,69(13):5383-5391.
[26] 苗亚萍,陈萍.SII联合ALI在晚期胃癌患者化疗联合免疫治疗疗效中的预测价值[D].宁夏:宁夏医科大学,2025.
[27] 霍俊杰,陈凤菊,段颖欣,等.基于CT影像组学构建胃癌新辅助免疫治疗联合化疗疗效的预测模型[J].中国肿瘤临床,2025,52(1):16-23.
[28] CHEN Z F,CHEN Y, SUN Y, et al.Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immun otherapy based on multi-modal data[J].Signal Transduct Targ et Ther,2024,9(1):222.
[29] Liu Y,Chen W,Rran R,et al. Deep learing based digital pathology for predicting treatment response to first-line PD-1 blockade in advanced gastric cancer[J].J Transl Med, 2024,22(1):438.
[30] GAO X J,MA T T,CUI J L,et al.A radiomics-based model for prediction of lymph node metastasis in gastric cancer [J].Eur J Radiol,2020,129:109069.
[31] ARORA A, ALDERMAN J E, PALMER J, et al. The value of standards for health datasets in artificial intelligence-bas ed applications[J].Nat Med,2023,29(11):2929-2938.
[32] 牛威.PD-L1单克隆抗体联合益生菌在胃癌中的治疗作用与机制[D].天津:天津医科大学,2021.
[2] KUS T,KOSE F,AKTAS G,et al.Prediction of peritoneal rec urrence in patients with gastric cancer: a multicenter study [J].J Gastrointest Cancer,2021,52(2):634-642.
[3] Topalian SL,Hodi FS,Brahmer JR,et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer[J]. N Engl J Med,2012,366(26):2443-2454.
[4] Xu JM,Jiang HP,Pan YY,et al. Sintilimab plus chemothe rapy for unresectable gastric or gastroesophageal junction ca ncer:the ORIENT-16 randomized clinical trial[J].JAMA, 2023, 330(21):2064-2074.
[5] Janjigian YY,Shitara K,Moehler M,et al.First-line nivol umab plus chemotherapy versus chemotherapy alone for advan ced gastric, gastro-oesophageal junction,and oesophageal ade nocarcinoma(CheckMate 649):a randomised,openlabel,phase 3 trial[J].Lancet,2021,398(10294):27-40.
[6] Janjigian YY,Kawazoe A,Yañez P,et al. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer[J].Nature,2021,600(7890):727-730.
[7] ChaoJ,Fuchs CS,Shitara K,et al.Assessment of pembroliz umab therapy for the treatment of microsatellite instability -high gastric or gastroesophageal junction cancer among pati ents in the KEYNOTE-059,KEYNOTE-061,and KEYNOTE-062 clinic al trials[J].JAMA Oncol,2021,7(6):895-902.
[8] Zeinalian M, Hashemzadeh-Chaleshtori M, Salehi R, et al. Clinical Aspects of Microsatellite Instability Testing in Colorectal Cancer[J].Adv Biomed Res,2018,7:28.
[9] Akagi K,Oki E,Taniguchi H,et al. Realworld data on micr osatellite instability status in various unresectable or metas tatic solid tumors[J]. Cancer Sci,2021,112(3):1105-1113.
[10] Muro K,Kawakami H,Kadowki S,er al. 1513MO A phase Ⅱ study of nivolumab plus low dose ipilimumab as first-line the rapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor: First results of the NO LIMIT study (WJOG13320G/CA209-7W7)[J].Ann Oncol,2023,34:s852-s853.
[11] HABER J E,Partners and pathways: reparing a doublestrand break[J].Trends in Genetics,2020,16(6):259-264.
[12] 任南,吕雪洁,何陈周,等.胃癌预后全基因组关联分析[J].中国公共卫生,2023,39(2):7.
[13] Lee Y,Kim HD,Lee SY.et al.Predictive value of homolog ous recombination-related gene mutations in survival outco mes of first-line nivolumab plus chemotherapy for gastric cancer[J].Gastric Cancer (2025).https://doi.org/10.1007/s10120-025-01648-0.
[14] 娄俊,易韵.70例卵巢癌患者治疗期间外周血T淋巴细胞亚群测定的临床意义[J].实用癌症杂志,2022,37(5):780-782.
[15] Al-Shibli KI, Donnem T, Al-Saad S, et al. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer[J].Clinical cancer research: an off icial journal of the American Association for Cancer Research,2008,14(16):5220-7.
[16] 鲍千红,吕凌云,张伟群,等.过敏性鼻炎患者血清中炎症因子、免疫球蛋白及T淋巴细胞亚群水平检测及分析[J].中国卫生检验杂志,2020,30(21):2614-2616.
[17] Lowery FJ, Goff SL, Gasmi B, et al. Neoantigen-specif ic tumor-infiltrating lymphocytes in gastrointestinal cance rs:a phase 2 trial[J].Nat Med. 2025 Apr 1.
[18] Zhang N,Cao M,Duan Y,et al.Prognostic role of tumorin filtrating lymphocytes in gastric cancer: a metaanalysis and experimental validation[J].Arch Med Sci,2020,16(5):1092-1103.
[19] 彭春伟,刘广杰,余昌俊.胃癌患者血清IL-6、IL-8、TNF-α表达水平及其临床意义分析[J].中国医学前沿杂志(电子版),2019,11(07):125-129.
[20] 冯宁,尚红港.肿瘤坏死因子-α、白介素-6和白介素-8检测在胃癌中的临床价值[J].肿瘤基础与临床,2021,34(3):244-247.
[21] 王晓倩,李丹丹,王丹,等.乳腺癌4T1细胞中过表达鼠白介素-10对宿主抗肿瘤免疫应答的影响[J].山西医科大学学报,2021,52(5):559-564.
[22] 仇海乐,戎冬文,贾军梅.肿瘤坏死因子-α瘤内注射联合化疗治疗晚期非小细胞肺癌疗效观察 [J].肿瘤基础与临床,2020,33(5):404-406.
[23] 王馨焱,代虎威,刘晓玲.外周血细胞因子预测晚期胃癌抗PD-1治疗的疗效及预后[J].现代肿瘤医学,2023,31(15):2872-2878.
[24] 谢晓虹,骆玉霜.基于细胞因子构建初始不可切除或晚期胃癌患者接受热疗联合免疫及化疗的疗效预测模型[D].青海:青海大学,2024.
[25] Ray-Coquard I,Cropet C,Van Glabbeke M,et al. Lymph openia as a prognostic factor for overall survival in advanced carcinomas,sarcomas, and lymphomas[J].Cancer Res,2009,69(13):5383-5391.
[26] 苗亚萍,陈萍.SII联合ALI在晚期胃癌患者化疗联合免疫治疗疗效中的预测价值[D].宁夏:宁夏医科大学,2025.
[27] 霍俊杰,陈凤菊,段颖欣,等.基于CT影像组学构建胃癌新辅助免疫治疗联合化疗疗效的预测模型[J].中国肿瘤临床,2025,52(1):16-23.
[28] CHEN Z F,CHEN Y, SUN Y, et al.Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immun otherapy based on multi-modal data[J].Signal Transduct Targ et Ther,2024,9(1):222.
[29] Liu Y,Chen W,Rran R,et al. Deep learing based digital pathology for predicting treatment response to first-line PD-1 blockade in advanced gastric cancer[J].J Transl Med, 2024,22(1):438.
[30] GAO X J,MA T T,CUI J L,et al.A radiomics-based model for prediction of lymph node metastasis in gastric cancer [J].Eur J Radiol,2020,129:109069.
[31] ARORA A, ALDERMAN J E, PALMER J, et al. The value of standards for health datasets in artificial intelligence-bas ed applications[J].Nat Med,2023,29(11):2929-2938.
[32] 牛威.PD-L1单克隆抗体联合益生菌在胃癌中的治疗作用与机制[D].天津:天津医科大学,2021.
Copyright © 2025 黄敏, 范宝化, 都学元, 陈蓉, 姜军
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License