Tumor-immune plasticity: defining the dynamic interactions shaping immunotherapy response, escape and toxicity

Cancer immunotherapy has revolutionized anti-tumor care, yet variable patient responses, innate/acquired treatment escape, and immune-related toxicities remain major clinical barriers. Traditional research has largely characterized static immune states within the tumor microenvironment (TME), failing to capture the adaptive and reciprocal crosstalk between tumor and immune cells—termed tumor-immune plasticity—that underpins treatment outcomes. Tumor cells dynamically remodel their phenotype and the TME in response to immune pressure, while immune cells shift their functional states based on contextual TME cues, creating a bidirectional adaptive loop. This plasticity drives the transition between immune-sensitive and immune-evasive tumor states, and also modulates the balance between anti-tumor immunity and systemic immune dysregulation that causes toxicity. Unraveling the dynamic nature of these interactions is critical to moving beyond static biomarker profiling and understanding the core drivers of immunotherapy success and failure.This research topic addresses the critical knowledge gap in defining how tumor-immune plasticity, rather than fixed immune or tumor states, governs immunotherapy response, escape and toxicity. A core challenge is identifying the key dynamic cellular and molecular interactions that tip the balance toward anti-tumor immunity, immune evasion, or off-target immune activation. The goal is to elucidate the mechanistic underpinnings of tumor-immune plasticity across solid and hematologic malignancies, including the signaling pathways, epigenetic reprogramming, and TME cues that drive adaptive phenotypic shifts in both tumor and immune cells. Leveraging recent advances in longitudinal single-cell omics, spatial transcriptomics, and functional in vivo plasticity models, this topic aims to map the dynamic trajectories of tumor-immune interactions during immunotherapy. Additionally, it seeks to explore novel translational strategies to target or harness plasticity—such as adaptive combination therapies, plasticity-modulating agents, or personalized dynamic monitoring—to enhance treatment response, reverse immune escape, and mitigate immune-related toxicities. Ultimately, this research will redefine immunotherapy development by centering dynamic plasticity over static profiling, enabling the design of more precise, adaptive interventions that align with the ever-evolving tumor-immune interface.This research topic centers on tumor-immune plasticity as the core driver of immunotherapy outcomes, focusing on dynamic tumor-immune interactions and their translational potential for improving treatment efficacy and safety. Contributors are invited to address the following specific themes:• Mechanistic drivers of tumor-immune plasticity in solid and hematologic malignancies• Longitudinal profiling of dynamic tumor and immune cell state shifts during immunotherapy• Plasticity-mediated immunotherapy escape and strategies to reverse adaptive tumor evasion• Links between tumor-immune plasticity and immune-related adverse event development• Novel experimental and computational models to study dynamic tumor-immune crosstalk• Translational approaches targeting or harnessing plasticity for improved immunotherapyWe welcome original research articles, comprehensive review papers, and short communications presenting novel mechanistic findings, longitudinal profiling data, preclinical models of plasticity, or promising translational strategies in this emerging field.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.Please note that Dr. Natalia Neparidze has received research funding to the institution from Glaxo-Smith-Kline and Johnson & Johnson; and has consulted for and holds an equity interest in Cellsbin, Inc. Topic editors: Natalia Neparidze, Zhihui Wang, Gaopeng Li Source: https://www.frontiersin.org/research-topics/79422/tumor-immune-plasticity-defining-the-dynamic-interactions-shaping-immunotherapy-response-escape-and-toxicity