Research ArticleCancer

Control of brain tumor growth by reactivating myeloid cells with niacin

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Science Translational Medicine  01 Apr 2020:
Vol. 12, Issue 537, eaay9924
DOI: 10.1126/scitranslmed.aay9924

An old vitamin’s new tricks

Although innate immune cells are typically present inside tumors, they often have an inactive phenotype such that they are ineffective at killing the cancer cells or even promote tumor growth. Sarkar et al. discovered that it may be possible to reprogram these cells to a more active type using niacin (vitamin B3). The authors showed that niacin-exposed monocytes can inhibit the growth of brain tumor–initiating cells. Moreover, niacin treatment of intracranial mouse models of glioblastoma increased monocyte and macrophage infiltration into the tumors, stimulated antitumor immune responses, and extended the animals’ survival, especially when combined with the chemotherapeutic drug temozolomide.

Abstract

Glioblastomas are generally incurable partly because monocytes, macrophages, and microglia in afflicted patients do not function in an antitumor capacity. Medications that reactivate these macrophages/microglia, as well as circulating monocytes that become macrophages, could thus be useful to treat glioblastoma. We have discovered that niacin (vitamin B3) is a potential stimulator of these inefficient myeloid cells. Niacin-exposed monocytes attenuated the growth of brain tumor–initiating cells (BTICs) derived from glioblastoma patients by producing anti-proliferative interferon-α14. Niacin treatment of mice bearing intracranial BTICs increased macrophage/microglia representation within the tumor, reduced tumor size, and prolonged survival. These therapeutic outcomes were negated in mice depleted of circulating monocytes or harboring interferon-α receptor–deleted BTICs. Combination treatment with temozolomide enhanced niacin-promoted survival. Monocytes from glioblastoma patients had increased interferon-α14 upon niacin exposure and were reactivated to reduce BTIC growth in culture. We highlight niacin, a common vitamin that can be quickly translated into clinical application, as an immune stimulator against glioblastomas.

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