Biobanks of primary cultures enriched with Lung Cancer Stem Cells (CSC) and adapted immune cells: targeting lipid metabolism and correlations patients risk factors
Componente | Categoria |
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Christian Napoli | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
Maurizio Alimandi | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
Simona Petrucci | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
Alberto Ricci | Componenti strutturati del gruppo di ricerca / Structured participants in the research project |
Claudia De Vitis | Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group |
Componente | Qualifica | Struttura | Categoria |
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Fattore Luigi | PhD | Istituto Pasteur, Fondazione Cenci-Bolognetti laboratorio affiliato Dipaartimento di Medicina Clinica e Molecolare | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships |
Bruschini Sara | PhD student | Magna Greace Catanzaro | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships |
Ruggero Ciro Francesco | PhD | IRCCS -IFO | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships |
Alessandro Zerbetto | specializing in hygiene | Public Health and Infectious Diseases LS/_8 | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships |
Massimiliano Bassi | Specializing in thoracic surgery | Policlinico Umberto I, Sapienza University of Rome | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships |
Dandrilli Antonio | Medical Doctor in thoracic surgery | Azienda Ospedaliera Sant'andrea | Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships |
Immunotherapy with immune checkpoint inhibitors (ICIs) has recently shown significant clinical efficacy with long term survival benefit in Non Small Cell Lung Cancer patients, although a main issue remains the high rate of failures. Significant efforts are directed to understand the mechanisms responsible for ICIs failures and to intervene on them in order to increase the proportion of responding patients. In this context there is mounting evidence that Cancer Stem Cells (CSCs) are by themselves weakly immunogenic. In addition, CSCs may contribute to the establishment of an immunosuppressive tumor micro-environment through their cross talk with protumorigenic cell types. Our laboratory has a multi- year expertise in the study of CSCs from adenocarcinoma of the lung. Major focus has been the demonstration that SCD1, the enzyme responsible of the synthesis of Monounsaturated Fatty Acids, plays an important role in lung CSCs propagation and survival, contributing to the activation of the beta-catenin and YAP/TAZ pathways. Our recent preliminary data suggest that lung CSCs hold an immune-evasive phenotype and that inhibiting both monounsaturated fatty acids and cholesterol synthesis, induces a pro-inflammatory and pro-immunogenic phenotype.
We hypothesize that a deeper understanding of the immune-evasive properties of lung adenocarcinoma CSCs and of their immune-suppressive pathways and analyze the patient risk factors (genetic susceptibility, poor diet, occupational exposures and air pollution may act independently or in concert with tobacco smoking in shaping the descriptive epidemiology of lung cancer genetic), as well as of CSCs ability to modify tumour micro-environment. Is needed because this may led to the identification of targets and pharmacological tools able to revert immune-evasion. Therefore, we believe that inhibition of lipid metabolic pathways could enhance immunogenicity of CSCs, likely improving ICI-based therapies.