Laboratory Biomarkers and Immunological Modulation of Sintilimab in Gastric Cancer: A Meta-Analysis Focused on Tumor Markers and T-Cell Subsets
Sintilimab for Gastric Cancer: Efficacy, Markers, and Safety
Sažetak
Background: Sintilimab, a PD-1 inhibitor, has emerged as a promising immunotherapeutic agent in gastric cancer. However, its impact on laboratory-based biochemical markers and immune indicators remains underexplored. This meta-analysis aimed to evaluate the changes in tumor biomarkers and T lymphocyte subsets, alongside clinical outcomes, in patients receiving sintilimab.
Methods: A comprehensive literature search of randomized controlled trials (2022–2025) was conducted across CNKI, Wanfang, VIP, and PubMed databases. Primary outcomes included serum tumor markers (CEA, CA199, CA242) and immune parameters (CD4⁺, CD8⁺ T-cell subsets). Secondary outcomes were ORR, DCR, OS, PFS, and adverse reactions. RevMan 5.2 was used for meta-analysis.
Results: Sixteen studies were included. Sintilimab treatment significantly reduced CEA, CA199, and CA242 levels (P < 0.0001), and favorably modulated immune subsets by increasing CD4⁺ and decreasing CD8⁺ cell counts. These biochemical and immunological improvements correlated with higher ORR, DCR, and OS, without increased adverse events (P > 0.05).
Conclusion: Sintilimab confers measurable improvements in key laboratory-based tumor and immune biomarkers, supporting its utility in clinical biochemical monitoring and immunotherapy response evaluation for gastric cancer patients. These findings align with the emerging integration of immunotherapy and biochemical diagnostics in oncology.
Reference
2. Yin B, Dong B, Guo X, Wang C, Huo H. GABPA protects against gastric cancer deterioration via negatively regulating GPX1. J Med Biochem 2022; 41(3): 355-62.
3. Mei Y, Shi M, Zhu Z, Yuan H, Yan C, Li C, et al. Addition of sintilimab to nanoparticle albumin-bound paclitaxel and S-1 as adjuvant therapy in stage IIIC gastric cancer. Future Oncol 2022; 18(2): 139-48.
4. Wang Y, Li D. Predictive value of serum tumor markers (carcinoembryonic antigen, neuron-specific enolase, and squamous cell carcinoma antigen in non-small cell lung cancer patients treated with programmed cell death protein 1 inhibitors. J Med Biochem 2025; 44(3): 678-86.
5. Wei J, Guo X, Yang X, Liu J, Duan Q, Tan Y, et al. Sintilimab plus fluorouracil, leucovorin, oxaliplatin and docetaxel regimen as neoadjuvant therapy for resectable gastric cancer and biomarker exploration. Future Oncol 2023; 19(36): 2395-403.
6. Cai L, Qu L, Cheng Y, Zhang J, Li S, Wu S. Study on the therapeutic effect of sintilimab combined with modified DCF regimen on advanced gastric cancer and its impact on Th1/Th2 immune balance. Anti-Cancer Drug 2024; 35(8): 780-8.
7. Liu Z, Liu A, Li M, Xiang J, Yu G, Sun P. Efficacy and safety of sintilimab combined with trastuzumab and chemotherapy in HER2-positive advanced gastric or gastroesophageal junction cancer. Front Immunol 2025; 16: 1545304.
8. Zhang Z, Ning MY, Han D, Li L, Li ZZ. Hyperthermic Intraperitoneal Chemotherapy plus Intravenous Chemotherapy of Paclitaxel with or without Sintilimab in Gastric Cancer: A Comparative Study. J Oncol 2022; 2022: 3054485.
9. Huang X, Fang J, Huang L, Chen H, Chen H, Chai T, et al. SOX combined with sintilimab versus SOX alone in the perioperative management of locally advanced gastric cancer: a propensity score-matched analysis. Gastric Cancer 2023; 26(6): 1040-50.
10. Wang Zhengdong, Pan Cheng, Zhou Aiming, et al. Clinical study on the combination of sintilimab and albumin-bound paclitaxel for the treatment of advanced gastric cancer patients. Chinese Journal of Clinical Pharmacology 2024; 40(20): 2968-72.
11. Liu Zhao, Ren Yuchuan, Zhang Yapeng, et al. The short-term efficacy of sintilimab in combination with chemotherapy for advanced gastric cancer patients and its effects on serum CEA, Tim-3, sLAG-3, and T lymphocyte subpopulations. Hebei Medical Journal 2024; 30(2): 335-40.
12. Wei Chunyan and Song Lili. Clinical study on the combination of Xindili monoclonal antibody and modified DCF regimen for the treatment of advanced gastric cancer. Journal of Laboratory Medicine and Clinical Practice 2022; 19(14): 1970-4.
13. Jiao Fu-zhi, Chen Ya-rui, Ji Wei, et al. Near-term efficacy and safety assessment of PD-1 inhibitor combined with chemotherapy as a first-line neoadjuvant therapy for locally advanced gastric adenocarcinoma. China Drug Alert 2023; 20(3): 301-5.
14. Jiang Jiaxing, Feng Feng, Dai Wei, et al. Clinical efficacy of the combination of oxaliplatin and capecitabine chemotherapy with sintilimab in treating advanced gastric cancer. Clinical Military Medical Journal 2024; 52(8): 820-822+826.
15. Li Lu-Lu, Huang Ran-Xin, Zhang Rong, et al. The effects of sintilimab combined with albumin-bound paclitaxel on serum tumor marker levels and immune function in advanced gastric cancer. Clinical and Experimental Medicine Journal 2023; 22(22): 2384-7.
16. Lu Xiao, Lu Zhenjun, Jin Zhenjun, et al. Efficacy and safety of sintilimab combined with chemotherapy in the treatment of advanced gastric cancer. Clinical Journal of Drug Therapy 2023; 21(11): 47-51.
17. Hu Xueyang, Li Fanfan, Wu Hongyang, et al. Efficacy and safety of sintilimab in combination with chemotherapy for stage III to IV gastric/gastric-esophageal junction adenocarcinoma. Clinical Journal of Drug Therapy 2024; 22(7): 29-34.
18. Yang Bo and Jiang Qiufu. The mechanism of the combination therapy of sintilimab and DOS for treating advanced gastric cancer based on KDM3A expression analysis in cancer tissues. Hebei Medical Journal 2024; 46(19): 2904-8.
19. Zhang Shuai, Liu Liangliang, Huang Di, et al. Short-term efficacy and safety of cisplatin, capecitabine, and sintilimab as neoadjuvant therapy for locally advanced gastric cancer. Chinese Journal of Clinical Research 2025; 38(1): 33-36+41.
20. Zhang Xiaorui, Shan Haixia, Zhu Zhengqiu. Efficacy and safety of oxaliplatin and capecitabine in combination with sintilimab for first-line treatment of HER2-negative advanced gastric cancer. Chinese Journal of Clinical Research 2025; 38(01): 37-41.
21. Zhao Xiaomin, Ding Jie, and Wang Juan. The Impact of Xindili Monotherapy Combined with Platinum-based Chemotherapy on Immune Indicators and Survival of Patients with Advanced Gastric Cancer. Journal of North Sichuan Medical College 2025; 40(1): 25-8.
22. Guo H, Ding P, Sun C, Yang P, Tian Y, Liu Y, et al. Efficacy and safety of sintilimab plus XELOX as a neoadjuvant regimen in patients with locally advanced gastric cancer: A single-arm, open-label, phase II trial. Front Oncol 2022; 12: 927781.
23. Wang R, Zhang Z, Li D, Wu N, Peng Z. Association analysis of apoptosis-related gene caspase3, Integrin a subunit 1 and glutathione sulfur transferase M1 gene polymorphisms and susceptibility to gastric cardia carcinoma. J Med Biochem 2023; 42(3): 412-19.
24. Cui Dongfang, Zhou Sisu, Wang Eming, et al. Application of Combined Ultrasound Endoscopy and Serum CA199, PTN, and CCSA-2 Levels in the Diagnosis of Colorectal Cancer Patients. Modern Oncology Medicine 2021; 29(23): 4168-72.
25. Mei Peiyuan, Long Qinghong, and Liao Yongde. The anti-tumor mechanisms and clinical research progress of programmed death factor-1/procedural death factor ligand 1 inhibitors in neoadjuvant therapy for esophageal cancer. Chinese Journal of Experimental Surgery 2022; 39(8): 1439-49.
26. Zhang Long, Yue Aimin, Duan Hualing. Efficacy of Xindili monoclonal antibody combined with TACE for the treatment of advanced primary liver cancer and its effect on T lymphocyte subpopulations. Hainan Medical Journal 2025; 36(3): 327-31.
27. Chen Liangxin, Sun Peng, Hu Zhongzhou. The effects of sintilimab combined with chemotherapy on tumor markers and immune function in advanced non-small cell lung cancer. Journal of Laboratory Medicine and Clinical Practice 2022; 19(8): 1106-8.
28. Guo Fen, Wang Yu, Shi Jianming, et al. Clinical efficacy and safety of denizumab combined with chemotherapy for advanced gastric cancer based on real-world analysis. China Pharmaceutical 2023, 32(17): 111-5.
29. Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, et al. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. Bmj-Brit Med J 2022; 377: e068714.
30. Gao L, Tang L, Li X, Peng J, Hu Z, Liu B. Efficacy and safety of sintilimab combined with apatinib as third-line or above therapy for patients with advanced or metastatic gastric cancer. Anti-Cancer Drug 2024; 35(3): 277-83.
Sva prava zadržana (c) 2025 Xian Zhang, Qiang Zhao, Huafei Tang, Rui Qin, Ting Tian, Congying Li, Rui Ma
Ovaj rad je pod Creative Commons Autorstvo 4.0 međunarodnom licencom.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.