Creation of a 3D CRiMe scene to unravel Cytotoxicity Resistant Mechanisms in non-small cell lung cancer.

Project Details

Description

Non-small cell lung cancer remains the leading cause of cancerrelated deaths worldwide. Despite breakthroughs in antitumor immunotherapy, the majority of patients currently don’t show any durable benefit. As immunotherapy aims to stimulate the cancerkilling potential of cytotoxic T lymphocytes (CTLs), these clinical findings suggest that there is an urgent need to decipher which novel
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 instalment of CRMs a very dynamic process, for which proper CRM screening assays are lacking. Therefore, this project aspires to develop an innovative human 3D CRM
SCREENING ASSAY that enables 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 scientificallybased 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 potentially toxic immunotherapy combinations.
AcronymFWOAL1006
StatusActive
Effective start/end date1/01/2131/12/24

Flemish discipline codes

  • Analysis of next-generation sequence data
  • Applied immunology
  • Cancer biology
  • Cell, tissue and organ engineering
  • Cellular interactions and extracellular matrix

Keywords

  • immunotherapy
  • non-small cell lung cancer
  • resistance mechanisms
  • 3D spheroids
  • stromal cells
  • cancer-associated fibroblasts
  • myeloid cells
  • RNAseq
  • CRISPR-Cas9 technology