Remodeling the tumor microenvironment and rational combinations in early-stage cancer immunotherapy

Early-stage cancer immunotherapy represents a promising yet underexplored frontier in cancer research. While immunotherapeutic strategies have achieved significant breakthroughs in advanced malignancies, their integration and optimization in early-stage settings remain limited by biological complexity and clinical uncertainty. Compared to later-stage disease, early cancers often exhibit distinct immunological features — such as reduced tumor burden and less adaptive immune suppression — which may provide a more receptive context for intervention. Still, major challenges persist, including variable tumor microenvironments, the risk of immune escape during early progression, and unpredictable treatment responses. Recent research indicates that the interplay between tumor cells, stromal components, vasculature, and the immune system is critical in dictating both resistance and responsiveness to immunotherapeutic agents in early-stage cancer. Despite advances in uncovering microenvironmental factors, a comprehensive understanding of their role in shaping clinical outcomes is still lacking, particularly regarding how these insights can inform the design of more effective combination strategies.This Research Topic aims to deepen our understanding of how tumor microenvironment remodeling influences the efficacy of immunotherapies in early-stage cancer, and to identify how mechanism-driven combination interventions may enhance patient benefit. The objective is to bridge basic, translational, and clinical research by elucidating specific microenvironmental determinants — including immunological, stromal, vascular, and metabolic characteristics — that modulate early tumor–immune interactions. In particular, we seek to highlight studies that propose or validate actionable methods to reprogram the tumor microenvironment, identify biomarkers for patient stratification, inform optimal therapeutic timing, and ultimately improve durable clinical outcomes through better-tailored immunotherapeutic regimens.This Research Topic is focused on mechanistic, translational, and clinical investigations into tumor microenvironment remodeling and combination interventions in early-stage cancer. Submissions are welcome that address mechanisms, strategies, and outcomes related to microenvironment-directed and combination-based interventions in early-stage disease settings and their clinical translation. To advance this area, we invite contributions on topics such as:• Distinctive features of the tumor immune microenvironment in early-stage versus advanced cancers• Cellular, stromal, vascular, and metabolic mechanisms influencing tumor microenvironment remodeling• Tumor–immune interactions and barriers affecting immunotherapy responsiveness in early-stage disease• Mechanism-informed combination strategies for enhancing antitumor immunity• Studies linking microenvironmental properties to therapeutic response, patient stratification, or long-term remissionPlease note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic. Topic editors: Hongfei Jiang, Renshuai Zhang, Guanzhao Wu, Cuixia Lu Source: https://www.frontiersin.org/research-topics/79510/remodeling-the-tumor-microenvironment-and-rational-combinations-in-early-stage-cancer-immunotherapy