Main research areas
Pharmacological Targeting of Tumor Microenvironment in Lymphoma
Tumor-associated macrophages (TAMs) and hyperactivation of signaling pathways, such as the phosphoinositide 3-kinase (PI3K)/AKT pathway, are critically involved in the pathogenesis of lymphomas. Both the δ and γ isoforms of PI3K are overexpressed by lymphoma cells as well as the tumor microenvironment (TME), thereby representing attractive therapeutic targets. We hypothesize that targeting signaling pathway may affect tumor cells as well as TME, ultimately leading to an antitumor response. Signaling inhibition may in fact exert a direct cytotoxic effect on lymphoma cells and reprogramme the TAMs from a protumor M2 phenotype to an antitumor M1 phenotype, thus reshaping the interplay between cancer cells and their TME. We use lymphoma cell lines and primary human macrophages to investigate the activity of signal transduction inhibitors in vitro and in vivo models of lymphoma. Pharmacological modulation is also investigated by RNA sequencing to elucidate the transcriptional changes of cancer cells and TME.
Liquid biopsy for disease outcome prediction and monitoring by circulating tumor DNA
Approaches for staging and response evaluation in Diffuse Large B-Cell Lymphoma (DLBCL) and Hodgkin Lymphoma (cHL) rely upon serial imaging assessments, using positron emission tomography (PET) and computed tomography (CT) scans. However, conventional imaging has suboptimal positive and negative predictive values. The use of cell-free fragments of tumor DNA that are shed into the bloodstream from tumor cells and can be easily and repeatedly obtained is emerging as an easy-to-obtain material assessing somatic cancer mutations. We hypothesize that high-throughput sequencing of circulating tumor (ct)DNA to analyze mutational heterogeneity, as well as genomic evolution (mutNGS), may represent an attractive tool to: (i) predict disease outcome; (ii) monitor disease response and minimal residual disease (MRD) as a surrogate marker for lymphoma chemosensitivity; (iii) Identify molecular determinants of chemorefractory patients; (iv) track clonal evolution-driven resistance to checkpoint inhibitors.
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Carmelo Carlo-Stella Publications
Selected Publications: Ghizzi A., Carlo-Stella C., Bossi M.T., Gorini M. "Overshoot" phenomenon in circulating granulocytic progenitor cell growth during remission of blast crisis in a case of CML. Haematologica 67:853-859, ...
