The role of the immune system against cancer was demonstrated as primary and acquired immunodeficiency is associated with increased susceptibility to cancer. Furthermore, the size of the immune infiltrate in primary tumor is a good prognosis for patient survival, explaining why blockage of immune checkpoint receptors is a very promising immunotherapy strategy. However, the occurrence of cancers and the resistance to blockage of these immune checkpoint receptors are the direct demonstration that tumor cells are capable of evading the host immune surveillance, and this ability to escape immune recognition and elimination, essential for cancer development, is now considered as a new feature in the hallmark of cancer. This is also true for glioblastoma multiforme, a very aggressive primary brain tumor, the cancer model under investigation in the lab. The natural killer (NK) cells and cytotoxic T lymphocytes (CTL) are the cytotoxic lymphocytes dedicated to engage and kill the cancer cells. A better understanding of factors regulating the dynamics of interaction between cancer cells and these cytotoxic lymphocytes is necessary to develop new therapeutics harnessing the patient own immune system to beat the disease.
In the lab, we focus on the role of immune inhibitory metabolites such as reactive oxygen species (ROS). ROS are pleotropic factors resulting from the cancer cell metabolic shift and the hypoxic microenvironment and they are strong candidates capable of orchestrating the reprogramming of the tumor microenvironment for tumor progression. Supporting this hypothesis, H2O2 modulates genes expression following the activation of redox responsive transcription factors. In addition, some of our preliminary data suggest that the cancer cell redox state could regulate lymphocyte function. Interestingly, we have also found that cancer cells, under the attack of the cytotoxic lymphocytes, experienced a massive ROS production that is necessary for their demise. Taken together ROS play a complex role in the dynamics of cancer-immune cell interaction. The Martinvalet’ lab investigates the role of the ROS in the cytotoxic immunity against glioblastoma multiforme both from the standpoint of the target cancer cells and the cytotoxic lymphocytes.
