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Multi-omics Analysis of Immune Cells Induced by Artificial Adjuvant Vector Cell (aAVC) Therapy in HPV-Positive Tumor-Bearing Mice [Spatial Transcriptomics]

ABSTRACT: Immune evasion by tumors highlights the need to activate both CTLs and NK cells against “immune-desert” type of tumor, yet the synergistic potential of dual activation in immune-desert tumors remains unclear. Here, we uncover a spatiotemporal synergy between NK cells and CTLs that drives functional antitumor effects in an immune-desert tumor model. Using a multi-omics imaging approach integrating spatial transcriptomics, scRNA-seq re-clustering, and multicolor flow cytometry, we show that vaccination rapidly reshapes lymphocyte localization and function in the tumor microenvironment (TME). Early activated IRF8+Klrg1+NK cell infiltration establishes a niche that guides subsequent antigen-primed CXCR3+CTL influx, accompanied by dendritic cell activation and inflammatory monocyte recruitment. This coordinated response relies on structural and chemotactic remodeling of the TME, facilitating NK-CTL interactions at the tumor margin. Our findings demonstrate how integrated multi-omics analyses can uncover previously inaccessible interactions and provide a framework for designing next-generation immunotherapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE312358 | GEO | 2026/06/21

REPOSITORIES: GEO

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Project description:Cervical cancer (CC) is one of the most common malignancy in women worldwide. It is characterized by a natural continuous phenomenon, that is, it is in the initial stage of HPV infection, progresses to intraepithelial neoplasia, and then develops into invasion and metastasis. Determining the complexity of tumor microenvironment (TME) can deepen our understanding of lesion progression and provide novel therapeutic strategies for CC. We performed the single-cell RNA sequencing on the normal cervix, intraepithelial neoplasia, primary tumor and metastatic lymph node tissues to describe the composition, lineage, and functional status of immune cells and mesenchymal cells at different stages of CC progression. A total of 59913 single cells were obtained and divided into 9 cellular clusters, including immune cells (T/NK cells, macrophages, B cells, plasma cells, mast cells and neutrophils) and mesenchymal cells (endothelial cells, smooth muscle cells and fibroblasts). Our results showed that there were distinct cell subpopulations in different stages of CC. High-stage intraepithelial neoplasia (HSIL) tissue exhibited a low, recently activated TME, and it was characterized by high infiltration of tissue-resident CD8 T cell, effector NK cells, Treg, DC1, pDC, and M1-like macrophages. Tumor tissue displayed high enrichment of exhausted CD8 T cells, resident NK cells and M2-like macrophages, suggesting immunosuppressive TME. Metastatic lymph node consisted of naive T cell, central memory T cell, circling NK cells, cytotoxic CD8+ T cells and effector memory CD8 T cells, suggesting an early activated phase of immune response. This study is the first to delineate the transcriptome profile of immune cells during CC progression using single-cell RNA sequencing. Our results indicated that HSIL exhibited a low, recently activated TME, tumor displayed immunosuppressive statue, and metastatic lymph node showed early activated phase of immune response. Our study enhanced the understanding of dynamic change of TME during CC progression and has implications for the development of novel treatments to inhibit the initiation and progression of CC.

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Multi-omics Analysis of Immune Cells Induced by Artificial Adjuvant Vector Cell (aAVC) Therapy in HPV-Positive Tumor-Bearing Mice [Spatial Transcriptomics]

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