{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:15:45Z","timestamp":1793837745390,"version":"4.6.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The tumor immune microenvironment plays a critical role in tumor progression and responses to immunotherapy. Nevertheless, its cellular complexity and heterogeneity remain incompletely understood. In this study, we employed high-resolution single-cell RNA sequencing on CD45+ immune cells isolated from ten syngeneic murine tumor models, representing seven distinct cancer types under treatment-na\u00efve conditions, thereby enabling a comprehensive profiling of tumor-infiltrating immune cells. We identified seven principal immune cell populations and provided an in-depth characterization of T cells, NK\/innate lymphoid cells, dendritic cells, monocytes\/macrophages, and neutrophils. Cross-species analyses further delineated conserved immune cell states and transcriptomic features within the T cell and monocyte\/macrophage compartments that are shared across syngeneic models and human tumors. To investigate the functional relevance of the predominant monocyte\/macrophage compartment and the notable presence of neutrophils in syngeneic tumors, we evaluated responses to anti-PD-1 therapy across various models and analyzed the enrichment of monocyte\/macrophage subsets in tumors that responded to treatment. Furthermore, we conducted neutrophil depletion experiments using anti-Ly6G antibodies, administered both as monotherapy and in combination with PD-1 blockade. Remarkably, an interferon-stimulated gene-high (ISG\n                    <jats:sup>high<\/jats:sup>\n                    ) monocyte subset was significantly enriched in models responsive to anti-PD-1 therapy. Neutrophil depletion resulted in variable antitumor effects across models but failed to enhance the efficacy of PD-1 blockade. In summary, our single-cell profiling offered a detailed atlas of the immune microenvironment across multiple syngeneic mouse tumor models, thereby enabling rational model selection for immuno-oncology studies. We uncovered an ISG\n                    <jats:sup>high<\/jats:sup>\n                    monocyte subset enriched in anti-PD-1 responsive models, and showed the context-dependent effects of neutrophil depletion on tumor immunity and immunotherapy, underscoring the heterogeneity and functional divergence of immune cell sublineages.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1676581","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T07:05:02Z","timestamp":1763103902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Single-cell atlas of the tumor immune microenvironment across syngeneic murine 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