Myeloid-derived suppressor cells (MDSC) are widely implicated in immune suppression associated with tumor progression and chronic inflammation. However, very little is known about their possible role in tumor development. Here, we evaluated the role of MDSC in two spontaneous experimental models of lung cancer: inflammation associated lung cancer caused by chemical carcinogen urethane in combination with exposure to cigarette smoke (CS); and transgenic CC10Tg model not associated with inflammation. Exposure of mice to CS alone resulted in significant accumulation in various organs of cells with typical MDSC phenotype (Gr-1+CD11b+). However, these cells lacked immune suppressive activity and could not be defined as MDSC. When CS was combined with a single dose of urethane, it led to the development of tumor lesions in lungs within 4 months. By that time, Gr-1+CD11b+ cells accumulated in spleen and lung, had potent immune suppressive activity and thus can be defined as MDSC. In the CC10Tg model, accumulation of immune suppressive MDSC was observed only at 4 months of age, after the appearance of tumor lesions in lungs. Accumulation of MDSC in both models was abrogated in S100A9 knockout mice. This resulted in dramatic improvement of survival of mice in both models. Thus, CS results in expansion of immature myeloid cells lacking suppressive activity. Accumulation of bona fide MDSC in both models was observed only after the development of tumor lesions. However, MDSC played a major role in tumor progression and survival, which suggests that their targeting may provide clinical benefits in lung cancer.
- Received August 21, 2013.
- Revision received September 26, 2013.
- Accepted October 4, 2013.
- Copyright © 2013, American Association for Cancer Research.