Translational research in posttransplant malignancies
- Principle investigator:
- Ignacio Revuelta
- Contact details:
Cancer is one of the main cause of death in general and solid organ transplant populations, mainly in related to metastatic disease. Cancer rates are higher after solid organ transplantation compared with the general population, although with different fold of increase within tumors. Length and intensity of exposure to immunosuppressive therapy are clearly related to post-transplant malignancy risk, and that once cancer has developed, more intense immunosuppression can translate into more aggressive tumour progression in terms of accelerated growth and metastasis and lower patient survival. The effect in immunosurviellance and the direct effect of immunosuppressive therapy in tumor immune escape and in several oncogenic pathways lead to tumoral progression, angiogenesis and pre-metastatic niche formation.
The tumor immune evasion mechanisms in primary tumor and distant host tissue, and the limited range of metastatic sites attributed to each cancer type, suggest the presence of factors capable of molding immune responses at systemic level to activate pre- metastatic niche and ulterior settlement of metastasizing tumor cells.
The purpose of this specific programme of work will be to figure out the interconnection between primary tumor and premetastatic niche to prepare for metastatic colonization and invasion in transplant patients under immunosuppressive therapy.
The project is likely to involve some or all of the following techniques: Cell culture both in murine and human cells, Gene silencing/downregulation by siRNAs and shRNAs, FACs techniques, Nanobiotechnology, Molecular biology techniques, including gene expression analysis by real-time PCR and by microarray, Tissue histology and immunohistochemistry, Microscopy (including confocal microscopy), Oncogenic experimental models with conditional knockout mice generation.
The programme is a continuation of work published in Transplantation (Revuelta et al, 2012; and Gutiérrez-Dalmau, Revuelta et al, 2010), which has provided critical information on the molecular characterization of colorectal adenocarcinoma and nonmelanoma skin cancer in renal transplant recipients by evaluation the distinct phenotype of these tumors. In addition, we explored the role of some signaling pathways in the pathogenesis and behavior of cancer in transplant patients, such as TGF-β, VEGF, and mTOR signaling pathway, their relation with the immunosuppressive therapy used in solid organ transplantation, and the existence of mutation status of some genes.
The added value of the group in this framework is the experience in translational research in posttransplant malignancies. In last 10 years within the introduction of mTOR inhibitors in the solid organ transplant strategies and their known anti-neoplasic characteristics, we have been interested in the role of the immunosurviellance and the immunosuppressive therapy in oncogenic processes as proliferation, angiogenesis and metastasis development. We have contributed to highlight the important of the molecular characterization of the cancer in transplant patients.
Posttransplant cancer, solid organ transplant, immunosuppressive therapy, tumor immune escape, cancer exosomes.
The main challenge of this research is to conduct translational research investigating the role of cancer- released nanoparticles in the postransplant malignancies and metastasis development.
The desirable achievements include to identify the role of the cancer- released exosomes in the progression and metastatsis development in posttransplant malignancies of patients under different immunosuppressive therapies. As well as looking for new interactions between effector and regulatory immune cells and cancer cells through this cancer exosomes.
We expect that the researcher candidate that would incorporate in our group could work independently and contribute to the design and procedure in a team- driven bias.
We also expect from him/her to have the skills, abilities and knowledge to perform this work, set up and run experiments in consultation with the Principal Investigator, as well as to record, analyse and write up the results of experiments, ensuring that notebooks are kept fully up to date as a formal record of the research. All the results will be discussed in detail between the team members and supervisors.
Team strategic objective in IDIBAPS
Cancer is one of the main cause of death of solid organ transplant patients. The main goal of this Research Group is the clinical and molecular characterization of posttransplant neoplasia. We are focus our interest in the study of the mechanisms of cancer of the different immunosuppressive therapy used in organ transplantation altering several oncogenic pathways, as well as the impact of the immunosuerviellance in tumor immune escape. The ultimate goal leis in looking for new biomarkers in primary tumor and metastatic disease in solid organ transplantation.(Read eligibility criteria)