This review systematically summarizes recent advances in immunotherapy for solid tumors, providing direct guidance for studying mechanisms of immunotherapy resistance and designing biomarker-driven personalized therapies. It is particularly valuable for developing novel combination strategies to overcome primary or acquired resistance.
Literature Overview
The article, 'Advances in Cancer Immunotherapy for Solid Tumors,' published in the journal Advanced Science, systematically explores key breakthroughs in the field of solid tumor immunotherapy in recent years, covering the integrated application of novel immune checkpoint inhibitors, antibody engineering platforms, cell therapies, and vaccine strategies. The article reviews the expansion from classical CTLA-4 and PD-1/PD-L1 pathway blockade to emerging targets such as LAG-3 and TIGIT, analyzes the role of biomarkers such as dMMR, MSI-H, and TMB in tissue-agnostic therapy, and deeply discusses the prospects of immunotherapy in early-stage and perioperative settings. Meanwhile, the authors emphasize current challenges, including immune-related adverse events (irAEs), resistance mechanisms, and treatment optimization strategies, providing a clear roadmap for future translational research.Background Knowledge
1. Solid tumor immunotherapy still faces significant clinical challenges; most patients exhibit primary or acquired resistance, and immune checkpoint inhibitors have limited efficacy in brain metastases, low tumor mutational burden, or immune-desert tumors. Additionally, long-term use of ICIs may lead to irreversible irAEs, limiting their widespread application in early-stage diseases.
2. The current research bottleneck for PD-1/PD-L1-targeted therapy lies in the lack of effective predictive biomarkers to accurately identify beneficiaries, and single-target blockade is often insufficient to overcome the complex immunosuppressive microenvironment. Meanwhile, although secondary checkpoints such as TIGIT and TIM-3 show potential, phase III clinical trial results have not met expectations, suggesting possible links to antibody engineering design (e.g., Fc function) or targeting specificity.
3. The focus of this article is on integrating multidimensional therapeutic strategies, including bispecific antibodies, cell therapies, and vaccines, to enhance tumor-specific immune responses and reduce systemic toxicity. By analyzing key entities such as LAG-3, TMB, and neoantigens, it proposes that future efforts should center on mechanism-driven combination regimens and personalized treatment pathways, advancing the shift from a 'one-size-fits-all' approach to precision immunotherapy.
Research Methods and Experiments
The authors systematically integrated key clinical trials and fundamental research data from recent years through a comprehensive review, covering phase I–III randomized controlled trials (e.g., RELATIVITY-047, KEYNOTE-177, CheckMate-8HW), real-world evidence, and mechanistic studies. The research relied on biomarker analysis from human tumor samples (e.g., PD-L1 expression, dMMR status, TMB detection), dynamic monitoring of the immune microenvironment in mouse tumor models, and in vitro T-cell functional assays to validate the activity of novel antibodies or cell therapies. Notably, by comparing the efficacy and safety of different immune checkpoint inhibitor combinations in melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer, the study revealed the clinical potential and limitations of targets such as LAG-3 and TIGIT.Key Conclusions and Perspectives
Research Significance and Prospects
This study provides clear direction for drug development: future efforts should focus on multi-target synergistic interventions, such as bispecific antibodies or cell therapies combined with ICIs, to overcome resistance. Meanwhile, adaptive modifications of personalized cancer vaccines and CAR-T for solid tumors hold promise for enhancing T-cell infiltration and persistence.
At the clinical monitoring level, dynamic assessment of TMB, ctDNA clearance rates, and T-cell clonal diversity will help identify true responders and guide decisions on treatment duration and discontinuation.
For disease modeling, it is necessary to develop humanized mouse models that more closely mimic the human tumor immune microenvironment to simulate immunosuppressive networks and test novel combination regimens, thereby accelerating clinical translation.
Conclusion
This review comprehensively outlines the evolution of solid tumor immunotherapy from advanced to perioperative settings, emphasizing the central role of multimodal strategies in overcoming resistance and improving cure rates. By integrating emerging targets such as LAG-3 and TIGIT with biomarkers such as dMMR/MSI-H, clinical practice is moving toward more precise, personalized immune interventions. Breakthroughs in perioperative immunotherapy—such as achieving high pathologic complete response rates in melanoma—suggest future organ-preserving strategies that may reduce or even eliminate the need for surgery and radiotherapy. Meanwhile, optimized antibody engineering and innovative cell therapies offer new tools to enhance efficacy and safety. From bench to bedside, these advances are reshaping the care paradigms for solid tumors such as non-small cell lung cancer, colorectal cancer, and melanoma, propelling immunotherapy into a new era of moving from 'few responders' to 'potential cures.' Future research should focus on dynamic biomarker monitoring and mechanism-driven combination designs to achieve truly meaningful precision immuno-oncology.
