TNFSF4 (OX40L) expression and survival in locally advanced and metastatic melanoma.

TNFSF4 (OX40L) expression and survival in locally advanced and metastatic melanoma.

Publication date: Sep 09, 2019

Immunotherapy with checkpoint inhibitors revolutionized melanoma treatment in both the adjuvant and metastatic setting, yet not all metastatic patients respond, and metastatic disease still often recurs among immunotherapy-treated patients with locally advanced disease. TNFSF4 is a co-stimulatory checkpoint protein expressed by several types of immune and non-immune cells, and was shown in the past to enhance the anti-neoplastic activity of T cells. Here, we assessed its expression in melanoma and its association with outcome in locally advanced and metastatic disease. We used publicly available data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE), and RNA sequencing data from anti-PD1-treated patients at Sheba medical center. TNFSF4 mRNA is expressed in melanoma cell lines and melanoma samples, including those with low lymphocytic infiltrates, and is not associated with the ulceration status of the primary tumor. Low expression of TNFSF4 mRNA is associated with worse prognosis in all melanoma patients and in the cohorts of stage III and stage IIIc-IV patients. Low expression of TNFSF4 mRNAs is also associated with worse prognosis in the subgroup of patients with low lymphocytic infiltrates, suggesting that tumoral TNFSF4 is associated with outcome. TNFSF4 expression was not correlated with the expression of other known checkpoint mRNAs. Last, metastatic patients with TNFSF4 mRNA expression within the lowest quartile have significantly worse outcome on anti-PD1 treatment, and a significantly lower response rate to these agents. Our current work points to TNFSF4 expression in melanoma as a potential determinant of prognosis, and warrants further translational and clinical research.

Roszik, J., Markovits, E., Dobosz, P., Layani, A., Slabodnik-Kaner, K., Baruch, E.N., Ben-Betzalel, G., Grimm, E., Berger, R., Sidi, Y., Schachter, J., Shapira-Frommer, R., Avni, D., Markel, G., and Leibowitz-Amit, R. TNFSF4 (OX40L) expression and survival in locally advanced and metastatic melanoma. 24080. 2019 Cancer Immunol Immunother.

Concepts Keywords
Adjuvant Cancer immunotherapy
Determinant Immunotherapy
Immune Cells Metastasis
Immunotherapy Checkpoint inhibitor
Melanoma RTT
Metastatic Melanoma
MRNA Immune system
MRNAs Oncology
Neoplastic Cancer treatments
Primary Tumor Cancer
Prognosis Medicine
Quartile Clinical medicine
Sequencing Immunotherapy
Sheba Expression melanoma
Subgroup Melanoma lines melanoma
Ulceration Metastatic disease
Melanoma treatment

Semantics

Type Source Name
gene UNIPROT PDCD1
gene UNIPROT SPATA2
disease DOID Cancer
disease MESH Cancer
gene UNIPROT EHD1
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT TNFSF4

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