Biology subjects

Maldonado, J. A.

Publications and source records attributed to Maldonado, J. A..

2 recordsLinked to original sources

bioRxiv2025

Single-Cell Analysis of Meningiomas Reveals Mutation-Associated Tumor and Immune Cell Gene Expression Programs

Genomic and epigenetic profiling, particularly DNA methylation analysis, have refined the molecular classification of meningiomas and revealed marked intratumoral heterogeneity. To further characterize heterogeneity within and between patients, we analyzed meningiomas using single-cell RNA sequencing (n=11), whole-exome sequencing (n=9), and spatial transcriptomics (n=3). Single-cell analysis revealed six transcriptionally distinct tumor cell states that corresponded to unique biological processes. Integration of the single-cell data with published exome and bulk RNA sequencing data from a large cohort revealed significant associations among somatic variants, tumor cell states, and immunological signatures. Notably, NF2-altered tumors were enriched for an epithelial-to-mesenchymal transition (EMT) cell state and immune cells, whereas NF2-intact tumors were enriched for a sterol metabolism cell state. Spatial transcriptomic analysis confirmed co-localization of immune cells and EMT tumor cells. Comparisons with immune cells from other brain tumors and peripheral tissues highlighted immunological cell states specific to meningioma. Collectively, these findings refine our genetic and molecular understanding of meningioma heterogeneity and underscore the link between genotype and molecular phenotype.

cancer biology↗

bioRxiv2024

Combined inhibition of S100A4 and TIGIT suppresses late-stage breast cancer metastasis to the lung by activating T and NK cells

Cancer metastasis is responsible for approximately 90% of cancer-related deaths, but very few treatment options exist currently. While the role of S100A4 in promoting metastasis has been known for decades, this knowledge has not been translated in the clinic. Here, we report that a novel monoclonal antibody against the human S100A4 protein (S1004-11) effectively suppresses breast cancer metastasis in two different mouse models. Importantly, a novel combination of ant-TIGIT and S100A4-11 can suppress lung metastases even in late-stage disease after the lung premetastatic niche (PMN) has already been established similar to a stage when many breast cancer patients are diagnosed. Mechanistically, S1004-11 mAb treatment block the formation of PMN by suppressing neutrophil infiltration and activating natural killer (NK) and T cells in the lung. Single-cell RNA-sequencing and cell:cell communication analyses indicate that TIGIT signaling suppresses NK cells, which is reversed in S100A4-11 treated PMN. In summary, this study provides compelling evidence for a novel mechanism of S100A4 function in PMN formation and the feasibility of using S100A4-11 monoclonal antibody to suppress metastases at different stages of breast cancer progression.

cancer biology↗