November 6, 2014

Immune cell activity and melanoma

The activity of a certain factor in immune cells is essential for an anti-tumor response, emphasizing the need to consider the effects of anti-cancer therapies on immune cells.

Melanoma, the most lethal form of skin cancer, spreads aggressively and is often resistant to therapy. Melanoma tumor formation is driven in part by nuclear factor-kappa B (NF-kappaB)-mediated gene transcription, and loss of NF-kappaB activity can block melanoma tumor formation. However, NF-kappaB also plays a crucial role in immune cells.

In an October online edition of Cancer Research, first author Jinming Yang, Ph.D., corresponding authors Fiona Yull, D.Phil., and Ann Richmond, Ph.D., and colleagues detailed effects of blocking NF-kappaB activity in myeloid cells on “anti-tumor” immune responses. Disappointingly, mice with myeloid specific inhibition of NF-kappaB exhibited enhanced melanoma growth and metastasis. In contrast, enhancing NF-kappaB activity in myeloid cells resulted in impaired tumor growth and metastasis.

Thus, myeloid cell NF-kappaB activity is essential for mounting the optimal “anti-tumor” immune response, emphasizing the need to consider effects of anti-cancer therapies not only on tumor cells, but also on the immune cells in the tumor microenvironment.

This research was supported by grants from the TVHS Department of Veterans Affairs and from the National Institutes of Health (CA116021, CA068485).

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