AUTHOR=Yan Yalan , Lu Jiaan , Luo Huanyu , Wang Zizhang , Xu Ke , Wang Lexin , Wang Qin 

TITLE=Decoding immune low-response states in ovarian cancer: insights from single-cell and spatial transcriptomics for precision immunotherapy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1667464

DOI=10.3389/fimmu.2025.1667464

ISSN=1664-3224

ABSTRACT=Ovarian cancer represents a typically immune “cold” tumor, where obvious immunosuppression, spatial T-cell exclusion, and cellular dysfunction collectively limit immunotherapy effectiveness. Especially in high-grade serous ovarian carcinoma (HGSOC), the immune low-response state is driven by complex interactions among tumor-associated macrophages (TAMs), suppressive stromal networks, and the T-cell compartment (regulatory T cells, Tregs, and exhausted effector T cells). Emerging multi-omics technologies—particularly single-cell RNA sequencing and spatial transcriptomics—have showed the heterogeneity and spatial immune organization underlying this suppressed state. Here, we integrate these datasets to describe TAM phenotypes and spatial niches, T-cell exhaustion, Tregs accumulation, NK-cell dysfunction, and stromal barriers that enforce exclusion. We then derive phenotype-guided combination strategies to remodel the tumor microenvironment and improve responsiveness to immune checkpoint blockade. This synthesis provides a concise, multi-dimensional framework for precision immunotherapy and for overcoming resistance in immune-low ovarian cancers.