Loss of CD38 in the TME as well as inhibition of its enzymatic activity restrained outgrowth of primary melanoma generated by two transplantable models of melanoma, B16F10 and Ret-mCherry-sorted melanoma cells. Collectively, our results suggest that targeting CD38 in the melanoma TME provides a new therapeutic approach for melanoma treatment.
Dr. Reuven Stein from the Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel said, "Melanoma is the deadliest skin cancer."
The melanoma tumor mass is comprised of tumor cells and stroma, known as tumor microenvironment. The TME in cancers, including melanoma contains different types of cells including, endothelial cells, infiltrating immune cells and cancer-associated fibroblasts. However, due to the heterogeneity of tumor cells, even within a single tumor mass, this task is challenging.
An alternative, yet complementary approach for cancer therapy is to target the TME cells. CD38 is also expressed in TME cells of extracranial tumors e.g., macrophages, T-cells endothelial cells and fibroblasts. The effect of CD38 targeting on B16F10 tumor progression involved increased cell death and reduction in the amount of CAFs and blood vessels, suggesting that loss of CD38 affects melanoma outgrowth through these effects.
The Reuven Stein research team concluded, "Collectively, our results suggest that targeting CD38 in the melanoma TME may be a beneficial approach to treat melanoma both as a neoadjuvant treatment, to reduce tumor growth before resection of primary tumor, as well as for inhibiting the occurrence of metastasis."
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DOI - https://doi.org/10.18632/oncotarget.25737
Full text - https://www.oncotarget.com/article/25737/text/
Correspondence to - Reuven Stein - [email protected]
Keywords - CD38, melanoma, tumor microenvironment, primary tumor, metastasis
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