Microenvironment and Immunology MDSC and TGFb Are Required for Facilitation of Tumor Growth in the Lungs of Mice Exposed to Carbon Nanotubes

During the last decades, changes have been observed in the frequency of different histologic 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 etiologic 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 proinflammatory 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 myeloidderived suppressor cells (MDSC) and MDSC-derived production of TGFb, resulting in upregulated tumor burden in the lung. The production of TGFb 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 TGFb production by SWCNT-attracted and -presensitized MDSC. Cancer Res; 75(8); 1615–23. 2015 AACR.