Seminario IMIPP - "The role of the tumour microenvironment in disease resistance in ALK+ ALCL" - Rebekka J. S. Salzmann

All students, scholarship holders, biochemists, biologists, PhDs, and researchers are invited to attend the seminar that will take place on Monday, May 20th at 11:00 am (GMT -3) via the Google Meet platform. If you have any questions or issues, please contact us.

Presenter: Rebekka J. S. Salzmann
Supervisor: Prof: Lara Mussolin
Workplace: University of Padova, Istituto di Ricerca Pediatrica, Molecular Diagnostic of Non Hodgkin Lymphoma.
Title: "The role of the tumour microenvironment in disease resistance in ALK+ ALCL"
Background: Despite effective initial treatments, 30% of paediatric ALK+ ALCL patients experience relapse. Recently we demonstrated that patients with bad prognosis are characterized by a specific small RNA cargo in plasma EVs at diagnosis, shaping a tumour-supporting microenvironment by triggering cytokine release from macrophages. Here we explore the macrophage and ALK+ ALCL crosstalk.
Aims: We aim to identify soluble factors that are released by the tumour microenvironment and regulate tumour proliferation, migration, and resistance. Furthermore, we want to elucidate the affected downstream pathways, identify altered gene expression patterns, and metabolites that might serve as novel targets for treatment, diagnostics, or prognostics.
Results: The secretion of 15 out of 40 cytokines was elevated in M2 CM vs. NC. The expression of the corresponding cytokine receptors was confirmed by qPCR. The ALK+ ALCL cell line SupM2 showed an increased migration when treated with M2 CM than with NC. Expression of CXCL9 was decreased and PD-L1 and CCL2 expression was increased in K299 and SupM2 cells treated with M2 CM vs. NC.
Summary/Conclusion: The SupM2 increase in migration treated with M2 CM vs. NC suggests a higher level of aggressiveness. The decreased expression of CXCL9 - a key chemoattractant for immunocytes, the increase in PD-L1 expression - known to promote tumour progression by blocking the activity of T-cells and increase of CCL2 - attracting tumour infiltrating monocytes and skewing them towards the M2 phenotype indicates a pro-tumorigenic effect of M2 CM on ALK+ ALCL cells. Ongoing experiments such as functional assays, gene expression profiling and the application of a microfluidic chip will elucidate further the effect of macrophage released factors on ALK+ ALCL cells.