High resistance rate of melanoma to chemotherapy results in the development of other therapeutic strategies
such as immunotherapy. Discrepancies observed in clinical responses to immunotherapy suggest the presence of immune
polymorphisms and tumor escape mechanisms.
The objective of this study was to investigate the expression of B7-H3 and B7-H4 which are major stakeholders in
immune regulation, and of the death receptors TRAIL-R1 and TRAIL-R2 which play an important role in controlling
tumor cell proliferation and apoptosis. The correlation between the expression levels of these proteins and the clinical
outcome has also been assessed.
The expression level of the proteins was analyzed on 32 invaded LN samples and on 11 matching tumor cell lines.
Immunohistochemical staining and double fluorescent immunostaining on lymph node (LN) frozen sections were
performed, as well as flow cytometry on tumor cell lines.
The 4 proteins were expressed in all LN biopsies within a range from 40.6% for TRAIL-R1 to 87.5% for TRAIL-R2.
These 4 proteins were rarely expressed by the tumor cell lines except for TRAIL-R2 which was detected in 10 of the 11
cell lines. The expression of these proteins by tumor cell lines is not correlated with in vivo expression found in
immunohistochemistry (IHC). It raises the question of the role of the tissue environment in the expression of the proteins.
The expression levels of B7-H4, TRAIL-R1, and TRAIL-R2 using IHC were correlated with overall survival. In vivo,
high expression levels of B7-H4, TRAIL-R1 or TRAIL-R2 appear as poor prognostic factors.