The tumor microenvironment (TME) is a living system. Cancer cells, immune cells, stromal populations, and vasculature interact in space and time, and these interactions change as tumors grow and as therapies apply pressure. This continuous remodeling can weaken anti-tumor immunity and is increasingly recognized as a major cause of resistance to immunotherapy.
This Research Topic brings together studies that use spatial transcriptomics and other spatially resolved approaches, including multiplex imaging, spatial proteomics, and single-cell methods with spatial reconstruction, to examine the TME in situ. We are particularly interested in work that connects tissue architecture to function: how cellular neighborhoods form, how immune cells are recruited or excluded, and how tumor–immune–stroma communication shapes response to treatment.
We welcome original research, methods papers, and reviews that identify spatial programs linked to response or resistance to immune checkpoint blockade and other immunotherapies, propose spatial biomarkers with clinical relevance, and uncover mechanisms that can be targeted therapeutically. A core emphasis is on reversal strategies: combination and sequential approaches that reprogram suppressive myeloid and stromal states, reduce fibroblast/ECM barriers, improve immune trafficking, and address metabolic and cytokine/chemokine constraints within tumors.
Overall, the goal of this Research Topic is to use spatial biology to clarify how resistance emerges, how it can be predicted, and how the TME can be redirected toward more effective and durable anti-tumor immune responses.
Keywords / areas of interest
Spatial profiling across tumor types and along the treatment timeline (including longitudinal cohorts)
Spatial biomarkers for response, resistance, relapse, and immune remodeling
Immune exclusion, exhaustion, antigen presentation defects, and tertiary lymphoid structures
Myeloid, fibroblast, endothelial, and ECM-driven mechanisms of immune suppression
Computational methods for spatial analysis and spatial multi-omic integration
TME-directed interventions that restore immunotherapy sensitivity
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Classification
Clinical Trial
Community Case Study
Data Report
Editorial
FAIR² Data
FAIR² DATA Direct Submission
Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.
Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
