Poster Presentation 27th Lorne Cancer Conference 2015

Oxidative burst produced by the NOX2 complex does not play a role in methylcholanthrene induced sarcoma development (#198)

Maarten A Ligtenberg 1 , Özcan Çınar 1 , Rikard Holmdahl 2 , Rolf Kiessling 1
  1. Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet,, Stockholm, Sweden
  2. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

Reactive Oxygen Species (ROS) produced by NOX2 complex are essential for proper immune cell function and immunomodulation. Classically, NOX2 in phagocytic cells produce super oxide to clear bacterial infection. Oxidative stress has been shown to modulate immune cell function, and is one of the key immune suppressive mechanisms, in MDSCs and Tregs, used to suppress T cell and NK cell effector functions. The tumor microenvironment is infiltrated by immune suppressive cells that are recruited from the periphery or polarized in the tumor microenvironment that in turn are responsible for blunting anti-tumor immunity. In this study we aimed at examining the role of oxidative burst by immune suppressive cells in a methylcholanthrene induced sarcoma model. Superoxide production by NOX2 requires p47phox (NCF1) to organize the formation of the NOX2 complex on the cell membrane. Homozygous mutant mice (NCF1*/*) have a functional loss of super oxide burst while heterozygous mice (NCF1*/+) retain this key immune cell function. These mice were injected with methylcholanthrene intramuscularly (25µg) to induce the development of sarcomas. We found that functionality of NOX2 did not lead to a difference in tumor incidence. Immunomonitoring by flow cytometry in tumor bearing mice showed that infiltrating immune cells experience an increase in oxidative state. Furthermore, infiltrating T cells showed an increase in effector-memory cell phenotype markers in both NCF1*/* and NCF1*/+ mice. Tumors established from both NCF1*/* and NCF1*/+ mice were tested for their in vitro proliferative capacity as well as their resistance to cisplatin treatment. These findings indicate that NOX2 and oxidative burst does not play a key role in tumor development or immune cell infiltration in the methylcholanthrene induced sarcoma model.