TY - JOUR
TI - Quantitative assessment of Siglec-15 expression in lung, breast, head, and neck squamous cell carcinoma and bladder cancer
AU - Shafi, S.
AU - Aung, T.N.
AU - Xirou, V.
AU - Gavrielatou, N.
AU - Vathiotis, I.A.
AU - Fernandez, A.
AU - Moutafi, M.
AU - Yaghoobi, V.
AU - Herbst, R.S.
AU - Liu, L.N.
AU - Langermann, S.
AU - Rimm, D.L.
JO - Laboratory Investigation
PY - 2022
VL - null
TODO - null
SP - null
PB - Springer Nature BV
SN - 0023-6837, 1530-0307
TODO - 10.1038/s41374-022-00796-6
TODO - null
TODO - 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.
ER -