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Strategic integration of immunotherapy with chemotherapy, radiotherapy, and targeted therapy in gastric cancer management: A systematic review
Yashwant Kumar Ratre, Nilabh Ghritlahre, Babita Pande, Tarun Sahu, Lakkakula Suhasini Sahithi, Shashikant Swarnkar, Henu Kumar Verma
Yashwant Kumar Ratre, Lakkakula Suhasini Sahithi, Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495001, Chhattisgarh, India
Nilabh Ghritlahre, Department of Physiology, Pandit Jawahar Lal Nehru Medical College, Raipur 492001, Chhattisgarh, India
Babita Pande, Life Science, Pt. Ravishankar Shukla University, Raipur 492001, Chhattisgarh, India
Tarun Sahu, Department of Physiology, All India Institute of Medical Science, Raipur 492001, Chhattisgarh, India
Shashikant Swarnkar, Department of Biochemistry, Chandulal Chandrakar Memorial Government Medical College, Bhilai 490024, Chhattisgarh, India
Henu Kumar Verma, Department of Bioscience and Biomedical Engineering, Indian Institute of Technology, Bhilai 491002, Chhattisgarh, India
Co-first authors: Yashwant Kumar Ratre and Nilabh Ghritlahre.
Author contributions: Verma HK contributed to the conceptualization, investigation and supervision; Ghritlahre N, Ratre YK, Sahithi LS, and Swarnkar S contributed to the methodology; Pande B and Verma HK contributed to the software; Sahu T, Ghritlahre N, Pande B, Ratre YK, Sahithi LS, and Swarnkar S contributed to the article search and writing the original draft; Ghritlahre N, Ratre YK, Pande B, and Sahu T contributed to the writing, reviewing, and editing of the manuscript.
AI contribution statement: AI tools (Grammarly) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Henu Kumar Verma, Assistant Professor, Department of Bioscience and Biomedical Engineering, Indian Institute of Technology, Kutelabhata, Bhilai 491002, Chhat
tisgarh, India.
henu.verma@yahoo.com
Received: October 27, 2025
Revised: December 22, 2025
Accepted: February 10, 2026
Published online: June 14, 2026
Processing time: 215 Days and 17.2 Hours
BACKGROUND
Gastric cancer (GC) poses significant treatment challenges due to late-stage diagnosis and the limited efficacy of conventional therapies. Immunotherapy, particularly immune checkpoint inhibitors such as pembrolizumab and nivolumab targeting the programmed death-ligand 1 (PD-L1) pathway, has shown promising results. Pembrolizumab is effective in PD-L1-positive tumors, while nivolumab improves overall survival and progression-free survival. Emerging therapies, including cancer vaccines and chimeric antigen receptor T-cell therapy, especially in human epidermal growth factor receptor 2 (HER2)-positive GC, offer additional avenues for improving outcomes.
AIM
To comprehensively evaluate the current evidence on the strategic integration of immunotherapy with chemotherapy, radiotherapy, and targeted therapies in the management of GC.
METHODS
This systematic review was conducted by analyzing clinical studies and trials on the integration of immunotherapy with chemotherapy, radiotherapy, and targeted therapy in GC. Databases such as PubMed, MEDLINE, and clinical trial registries were searched for studies published till June 2025. The review focused on combination strategies, treatment sequencing, molecular mechanisms, and the clinical impact of integrated therapies.
RESULTS
Evidence suggests that combining immunotherapy with chemotherapy exploits synergistic mechanisms, including immunogenic cell death and modulation of the tumor microenvironment. Similarly, the integration of immunotherapy with radiotherapy leverages the abscopal effect, enhancing systemic anti-tumor responses. Clinical trials involving combinations of immunotherapy with targeted therapies such as HER2, vascular endothelial growth factor receptor, and epidermal growth factor receptor inhibitors demonstrate improved survival outcomes in advanced GC. However, the optimal sequencing, dosing, and patient selection remain areas of active investigation.
CONCLUSION
The findings underscore the potential of immunotherapy, either alone or in combination with chemotherapy, radiotherapy, and targeted therapy, to transform GC management. Optimizing combination strategies and identifying predictive biomarkers are essential for improving therapeutic efficacy and patient outcomes. Future research should focus on refining these approaches to enhance survival and quality of life for patients with GC.
Core Tip: Gastric cancer remains challenging to treat due to late diagnosis and limited response to standard therapies. Immunotherapy, especially programmed cell death protein 1/programmed death-ligand 1 inhibitors like pembrolizumab and nivolumab, has shown promising results in improving survival. This systematic review emphasizes the benefits of integrating immunotherapy with chemotherapy, radiotherapy, and targeted therapy to enhance antitumor efficacy through mechanisms such as immunogenic cell death and the abscopal effect. Future studies should focus on optimizing treatment sequencing, dosing, and biomarker-based patient selection to refine combination strategies and improve survival and quality of life in patients with gastric cancer.
