Pathology-Driven Biomarkers Emerge as Critical Tools for Predicting Immunotherapy Response in Solid Tumors
核心洞察
Cancer immunotherapy benefits only a subset of solid tumor patients, driving urgent need for reliable predictive biomarkers grounded in tissue-based pathology.
Pathology-driven approaches including PD-L1 (搜索), TILs, tertiary lymphoid structures, and spatial profiling offer direct insight into tumor immune contexture and therapeutic responsiveness.
A new Frontiers Research Topic collection seeks to bridge mechanistic biomarker discovery with clinical implementation, emphasizing reproducibility, scoring standardization, and multi-omics integration.
The transformative impact of cancer immunotherapy on solid tumor treatment has been tempered by a persistent challenge: only a fraction of patients achieve durable clinical benefit. In response, a growing body of research is turning to pathology-driven biomarkers as essential instruments for predicting therapeutic response, resistance, and long-term outcomes. A new Research Topic collection launched by Frontiers aims to consolidate and advance this critical area of translational oncology.
The collection, titled "Pathology-Driven Biomarkers of Cancer Immunity and Immunotherapy Response in Solid Tumors (搜索)," positions tissue-based evaluation at the center of precision immuno-oncology. Unlike circulating or computational surrogates, pathology provides direct information on tumor morphology, immune infiltration, the spatial organization of the tumor microenvironment, and the expression of clinically relevant immune-checkpoint molecules.
"Pathology plays a central role, as tissue-based evaluation provides direct information on tumor morphology, immune infiltration, spatial organization of the tumor microenvironment, and the expression of clinically relevant immune-checkpoint molecules," the editors state in their call for submissions.
A Multidimensional Biomarker Landscape
The Research Topic encompasses a broad spectrum of tissue-based markers, including established immune-checkpoint biomarkers such as PD-L1 (搜索), CTLA-4 (搜索), LAG-3 (搜索), and TIM-3 (搜索), alongside emerging targets. Beyond checkpoint expression, the collection will explore tumor-infiltrating lymphocytes (TILs), macrophage polarization, tertiary lymphoid structures, mismatch repair deficiency, microsatellite instability (MSI), tumor mutational burden (TMB), and oncogenic pathway–immune interactions.
A parallel Research Topic, "Biomarkers in Cancer Immunotherapy: Mechanisms, Efficacy Prediction, and irAE Management," further contextualizes the biomarker landscape by categorizing indicators into three main groups: tumor tissue biomarkers, peripheral blood non-invasive biomarkers, and gut microbiome-associated biomarkers. Together, these components constitute what the editors describe as "an integrated, multidimensional biomarker system for efficacy assessment."
Classical tissue biomarkers such as PD-L1 (搜索) expression, TMB, and MSI remain critical for patient selection, while blood- and microbiome-derived markers enable real-time, non-invasive monitoring. Pre-treatment biomarkers guide personalized therapy stratification, whereas intra- and post-treatment dynamics can predict treatment outcomes, durability of response, recurrence risk, and the potential development of immune-related adverse events (irAEs).
Bridging Discovery and Clinical Implementation
A defining feature of the pathology-focused collection is its emphasis on translational practicality. The editors have signaled particular interest in studies evaluating methodological reproducibility, scoring systems, interobserver variability, pre-analytical and analytical pitfalls, and the practical implementation of biomarkers in diagnostic pathology workflows.
The heterogeneity of immune biomarkers across primary tumors, metastatic sites, and treatment-related changes represents another key focus area, as does the role of spatial and digital pathology in improving immune profiling. These considerations reflect a broader recognition that biomarker discovery alone is insufficient—robust, reproducible, and clinically feasible assays are essential for meaningful patient impact.
Mechanistic Understanding and irAE Prediction
The companion Research Topic on biomarker mechanisms underscores the importance of understanding the immunological networks that drive biomarker changes and their interaction with the tumor microenvironment. "Understanding the immunological mechanisms that drive biomarker changes and their interaction with the tumor microenvironment is fundamental for advancing the next generation of rational, mechanism-based immunotherapies," the editors note.
Predicting immune-related adverse events represents a particularly pressing need. The considerable heterogeneity in therapeutic efficacy, low response rates across certain tumor types, and the emergence of unpredictable irAEs remain key barriers to broader clinical success. Biomarkers capable of identifying patients at risk for severe irAEs could significantly improve the risk-benefit calculus of immunotherapy.
Scope and Collaborative Vision
Both Research Topics welcome contributions spanning genitourinary, gynecologic, gastrointestinal, thoracic, breast, skin, and head and neck malignancies, with both tumor-specific and pan-cancer perspectives encouraged. The collections aim to bring together pathologists, oncologists, immunologists, molecular biologists, and translational researchers to provide an updated, clinically oriented overview of how pathology-based immune biomarkers can refine patient selection, guide therapeutic strategies, and support the development of next-generation immunotherapy approaches.
Notably, both initiatives explicitly exclude manuscripts consisting solely of bioinformatics or computational analysis of public databases without independent cohort or biological validation, underscoring the commitment to clinically grounded, verifiable research.