MDSC and TGF-{beta} are required for facilitation of tumor growth in the lungs of mice exposed to carbon nanotubes.

During last decades, changes have been observed in the frequency of different histological subtypes of lung cancer – one of the most common causes of morbidity and mortality – with a declining proportion of squamous cell carcinomas and an increasing proportion of adenocarcinomas, particularly in developed countries. This suggests the emergence of new etiological factors and mechanisms including those defining the lung microenvironment promoting tumor growth. Assuming that the lung is the main portal of entry for broadly used nanomaterials and their established pro-inflammatory propensities, we hypothesized that nanomaterials may contribute to changes facilitating tumor growth. Here we report that an acute exposure to single-walled carbon nanotubes (SWCNT) induces recruitment and accumulation of lung-associated myeloid-derived suppressor cells (MDSC) and MDSC-derived production of TGF-β resulting in up-regulated tumor burden in the lung. The production of TGF-β by MDSC requires their interaction with both SWCNT and tumor cells. We conclude that pulmonary exposure to SWCNT favors the formation of a niche that supports ingrowth of lung carcinoma in vivo via activation of TGF-β production by SWCNT-attracted and pre-sensitized MDSC.