Deciphering the immune microenvironment of rare cancers

Rare cancers encompass a heterogeneous group of malignancies characterized by low incidence and prevalence but, often, disproportionately high mortality rates and limited treatment avenues. Despite advances in cancer immunology, the immune microenvironment of rare cancers remains poorly characterized, hindering the identification of potential prognostic and predictive biomarkers, and the development of targeted therapies. Current research is rapidly expanding through the integration of high-dimensional approaches, including flow cytometry, single-cell transcriptomics, TCR/BCR profiling, and spatial multiomic analyses, yet many rare tumor entities and subtypes, such as bone and soft tissue sarcomas, glioblastoma, mesothelioma, and certain hematologic malignancies, remain underrepresented in immunological investigations. Recent studies have begun to unravel aspects of immune diversity, cellular interactions, and unique evasion strategies within these rare tumors, providing glimpses into novel therapeutic vulnerabilities and resistance mechanisms. However, a comprehensive and comparative understanding of the immune composition and functional dynamics across rare cancer types and clinical contexts remains limited, reflecting both the complexity and the unmet need within this field.This Research Topic aims to advance our knowledge by showcasing studies that elucidate the immune landscape of rare cancers across a broad spectrum of tumor types and subtypes. We seek contributions that utilize innovative immune profiling technologies, such as flow cytometry, single-cell sequencing (transcriptome, TCR, BCR), and spatial multiomic platforms, to dissect immune cell ecosystems, clonal dynamics, spatial compartmentalization, and immune evasion across tumor, stromal, and peripheral environments. Through this collective effort, we aspire to identify immune signatures linked to prognosis, relapse, and therapeutic response, and to foster new hypotheses for precision immunotherapy and biomarker development tailored specifically to rare cancer populations.The scope of this Research Topic encompasses original research, reviews, and methodological advancements that explore the immune microenvironment in rare cancers, as broadly defined by low incidence and/or prevalence but substantial clinical impact. We welcome submissions addressing, but not limited to, the following themes:• High-dimensional immune profiling of rare cancers (including flow, spectral, and mass cytometry)• Single-cell transcriptomic and immune repertoire sequencing to map cell states, clonal expansion, and antigen experience• Spatial transcriptomics and single-cell spatial multiomics to delineate immune–tumor architectural relationships and niche biology• Tumor-type–specific immune microenvironments in rare or under-studied malignancies• Translational studies linking immune profiles to outcomes, therapeutic responses, and biomarker discoveryPlease note that manuscripts consisting solely of bioinformatics or computational analysis of public omics databases that are not supplemented by relevant functional validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Topic editors: Su Yin Lim, Mauro G Tognon Source: https://www.frontiersin.org/research-topics/78578/deciphering-the-immune-microenvironment-of-rare-cancers