@article{3220742,
    title = "Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer",
    author = "Shafi, S. and Aung, T.N. and Xirou, V. and Gavrielatou, N. and Vathiotis, I.A. and Fernandez, A. and Moutafi, M. and Yaghoobi, V. and Herbst, R.S. and Liu, L.N. and Langermann, S. and Rimm, D.L.",
    journal = "Laboratory Investigation",
    year = "2022",
    publisher = "Springer Nature BV",
    issn = "0023-6837, 1530-0307",
    doi = "10.1038/s41374-022-00796-6",
    abstract = "Immune checkpoint blockade with programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has resulted in significant progress in the treatment of various cancer types. However, not all patients respond to PD-1/PD-L1 blockade, underscoring the importance of identifying new potential targets for immunotherapy. One promising target is the immune system modulator Siglec-15. In this study, we assess Siglec-15 expression in solid tumors, with a focus on lung, breast, head and neck squamous and bladder cancers. Using quantitative immunofluorescence (QIF) with a previously validated antibody, we found increased Siglec-15 expression in both tumor and immune cells in all the four cancer types. Siglec-15 was seen to be predominantly expressed by the stromal immune cells (83% in lung, 70.1% in breast, 95.2% in head and neck squamous cell and 89% in bladder cancers). Considerable intra-tumoral heterogeneity was noted across cancer types. As previously described for non-small cell lung cancer (NSCLC), Siglec-15 expression was seen to be mutually exclusive to PD-L1 in all the four cancer types, although this differential expression was maintained but somewhat diminished in head and neck squamous cell carcinoma (HNSCC). Siglec-15 was not prognostic either for overall survival (OS) or progression-free survival (PFS). In summary, we show broad expression of this potential immune modulatory target in a wide range of cancer types. These data suggest potential future clinical trials in these tumor types. © 2022, The Author(s), under exclusive licence to United States and Canadian Academy of Pathology."
}