Non-small cell lung cancer remains the leading cause of cancerrelated deaths worldwide. Despite magnificent breakthroughs in antitumor immunotherapy, the majority of patients currently don’t show any durable benefit. As immunotherapy aims to stimulate the cancer-killing potential of cytotoxic T lymphocytes (CTLs), these clinical findings suggest that there is an urgent need to decipher which other CTL-killing resistant mechanisms (CRMs) should be tackled to increase to overall efficacy of antitumor immunotherapy. Previous studies have linked CRMs to cancer cells as well as to the physical and immunosuppressive hindrance installed by their surrounding stromal cells. These make cancer-cell specific CTLmediated killing and installment of CRMs a very dynamic process, for which proper CRM screening assays are lacking. Therefore, this project aspires to develop an innovative murine and human 3D CRM SCREENING ASSAY that enables us to 1) induce novel cancer cell intrinsic CRMs, 2) evaluate the impact of stromal cells on the induction of cancer-cell intrinsic CRMs, and 3) validate the impact of the identified CRMs in vitro and in vivo. The knowledge gained from this project, will foster more scientifically-based clinical development of novel drugs and combinations that could be delivered together with current immunotherapies. In addition, this knowledge can provide valid biomarkers for patient selection prior to administration of expensive and toxic immunotherapy combinations.
|Short title or EU acronym||OZR opvangmandaat|
|Effective start/end date||1/10/19 → 30/09/21|
- cancer biology
Flemish discipline codes
- Cell, tissue and organ engineering