Insights into Chronic Inflammation-Induced Immunosuppression in Cancer: from Mouse to Human

Chronic inflammation is considered as the secret killer as it can lead to various life threatening complications including cancer. In addition, developing tumors by themselves can induce micro and macro chronic inflammatory environments. Under both circumstances, an immunosuppressive milieu ensues, mediated primarily by myeloid derived suppressor cells, which enable escape of the tumor from immune surveillance. In the course of our studies we explored the underlying mechanisms for the observed immunosuppression and demonstrated that such an environment suppresses not only the host’s immune system but also newly administered immune cells and vaccination-based therapies thus, limiting success of cancer immunotherapies. In addition, we discovered that chemotherapeutic drugs have adverse effects on the immunosuppressive environment and thus, dictate tumor regression or progression.

We are currently analyzing modalities/drugs that can neutralize the immunosuppressive environment and increase efficacies of given chemo- and immune-based therapies. We are also establishing a high-fidelity detection system using unique biomarkers for monitoring the host’s immune status modified by chronic inflammation that could predict success of given therapies and disease regression/progression. To this end, we are using various mouse models such as a pathology free model, inflammatory bowel disease and inducible colorectal cancer, all driven by chronic inflammation. The obtained results are then beeing “translated” to the clinic.

Our recent retrospective studies show the first proof of concept in humans; analyses of blood samples from cancer patients for the expression of the biomarkers that sense the host’s immune status prior to and following chemo- and immune-based therapies could predict therapy efficacies and success. Such studies could facilitate designing of innovative combinatorial strategies for cancer therapies and immune system monitoring towards establishing optimal personalized cancer treatments.