BACR 3: Statins as novel therapeutic agents in targeting TAMs within human NSCLC microenvironment
1Cancer Studies, University of Leicester, UK,2Biochemistry Department, University of Leicester, UK,3Toxicology Unit, University of Leicester, UK
Lung cancer is the most aggressive malignancy all over the world and number one killer in the UK. We and many other research groups believe that the heterogeneity of NSCLC is the main cause behind its aggressiveness; however the tumour microenvironment is genetically more stable than the tumour itself. A potential method to control this cancer is by targeting one of the most important components of the tumour microenvironment which is tumour associated macrophages (TAMs) which are of two types (M1& M2). TAMs appear to play a crucial role in tumour development, proliferation and metastasis, especially the M2 phenotype.
Human EX vivo explant model.
Initially we investigated the clinical evidence of statin's effect on the TAMs levels in patients with NSCLC and they were on statin treatment by using monoclonal anti CD68 antibody as a specific marker for evaluation of these TAMs in paraffin embedded tissue blocks. We found a strong association between statin use and TAMs level. We've analysed further the anatomical localization of these TAMs and correlate that with statin use and we found an association between statin use and anatomical localization of TAMs. We treated explants with statin and we used cPARP to detect the apoptotic activity and correlate that with macrophages' levels which are stained with CD68 within stroma and tumour.
We are aiming to investigate the efficacy of statins in targeting tumour associated macrophages (TAMs) within the microenvironment of human non-small cell lung cancer using a cholesterol modulating drug termed Atorvastatin.