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Tumoral CD105 promotes immunosuppression, metastasis, and angiogenesis in renal cell carcinoma

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Abstract

CD105 (endoglin) is a transmembrane protein that functions as a TGF-beta coreceptor and is highly expressed on endothelial cells. Unsurprisingly, preclinical and clinical evidence strongly suggests that CD105 is an important contributor to tumor angiogenesis and tumor progression. Emerging evidence suggests that CD105 is also expressed by tumor cells themselves in certain cancers such as renal cell carcinoma (RCC). In human RCC tumor cells, CD105 expression is associated with stem cell-like properties and contributes to the malignant phenotype in vitro and in xenograft models. However, as a regulator of TGF-beta signaling, there is a striking lack of evidence for the role of tumor-expressed CD105 in the anti-tumor immune response and the tumor microenvironment. In this study, we report that tumor cell-expressed CD105 potentiates both the in vitro and in vivo tumorigenic potential of RCC in a syngeneic murine RCC tumor model. Importantly, we find that tumor cell-expressed CD105 sculpts the tumor microenvironment by enhancing the recruitment of immunosuppressive cell types and inhibiting the polyfunctionality of tumor-infiltrating CD4+ and CD8+ T cells. Finally, while CD105 expression by endothelial cells is a well-established contributor to tumor angiogenesis, we also find that tumor cell-expressed CD105 significantly contributes to tumor angiogenesis in RCC.

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All data generated or analyzed during this study are included in the article and its supplementary information files.

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Acknowledgements

The authors thank Dr. Devin Lowe at the Department of Immunotherapeutics and Biotechnology, TTUHSC, for providing the CRISPR-Cas9 vector.

Funding

This work is supported by the National Institutes of Health (NIH) 1R15CA216205-01 grant to Laurence Wood.

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Authors and Affiliations

  1. Department of Immunotherapeutics and Biotechnology, Jerry H Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, USA

    Mariam Oladejo, Hong-My Nguyen, Hannah Seah, Arani Datta & Laurence M. Wood

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  1. Mariam Oladejo
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Contributions

LMW conceptualized the study. MO and LMW designed the experiments. MO carried out experiments, data analysis, preparation of figures, and manuscript drafting, HMN supported in orthotopic tumor modeling, HS performed scratch assay, and AD supported with FACS sorting. LMW acquired funding, provided supervision, and editing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Laurence M. Wood.

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The authors declare that they have no conflicting interests.

Ethical approval

All applicable international, national, and institutional standards for the care and use of experimental animals were followed. All studies involving animals were carried out in accordance with ethical standards of the Texas Tech University Health Sciences Center under the IACUC protocol number 17018.

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Oladejo, M., Nguyen, HM., Seah, H. et al. Tumoral CD105 promotes immunosuppression, metastasis, and angiogenesis in renal cell carcinoma. Cancer Immunol Immunother 72, 1633–1646 (2023). https://doi.org/10.1007/s00262-022-03356-5

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