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4. Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma

Author

Salaroglio, Iris C., Kopecka, Joanna, Napoli, Francesca, Pradotto, Monica, Maletta, Francesca, Costardi, Lorena, Gagliasso, Matteo, Milosevic, Vladan, Ananthanarayanan, Preeta, Bironzo, Paolo, Tabbò, Fabrizio, Cartia, Carlotta F., Passone, Erika, Comunanza, Valentina, Ardissone, Francesco, Ruffini, Enrico, Bussolino, Federico, Righi, Luisella, Novello, Silvia, Di Maio, Massimo, Papotti, Mauro, Scagliotti, Giorgio V., and Riganti, Chiara

Published
2019
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5. Supplementary Figure S15 from Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer

Author

Anobile, Dario P., primary, Salaroglio, Iris C., primary, Tabbò, Fabrizio, primary, La Vecchia, Sofia, primary, Akman, Muhlis, primary, Napoli, Francesca, primary, Bungaro, Maristella, primary, Benso, Federica, primary, Aldieri, Elisabetta, primary, Bironzo, Paolo, primary, Kopecka, Joanna, primary, Passiglia, Francesco, primary, Righi, Luisella, primary, Novello, Silvia, primary, Scagliotti, Giorgio V., primary, and Riganti, Chiara, primary

Published
2023
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6. Supplementary Table S3 from Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer

Author

Anobile, Dario P., primary, Salaroglio, Iris C., primary, Tabbò, Fabrizio, primary, La Vecchia, Sofia, primary, Akman, Muhlis, primary, Napoli, Francesca, primary, Bungaro, Maristella, primary, Benso, Federica, primary, Aldieri, Elisabetta, primary, Bironzo, Paolo, primary, Kopecka, Joanna, primary, Passiglia, Francesco, primary, Righi, Luisella, primary, Novello, Silvia, primary, Scagliotti, Giorgio V., primary, and Riganti, Chiara, primary

Published
2023
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7. Data from Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer

Author

Anobile, Dario P., primary, Salaroglio, Iris C., primary, Tabbò, Fabrizio, primary, La Vecchia, Sofia, primary, Akman, Muhlis, primary, Napoli, Francesca, primary, Bungaro, Maristella, primary, Benso, Federica, primary, Aldieri, Elisabetta, primary, Bironzo, Paolo, primary, Kopecka, Joanna, primary, Passiglia, Francesco, primary, Righi, Luisella, primary, Novello, Silvia, primary, Scagliotti, Giorgio V., primary, and Riganti, Chiara, primary

Published
2023
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9. Autocrine 17-β-Estradiol/Estrogen Receptor-α Loop Determines the Response to Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer

Author

Anobile, Dario P., primary, Salaroglio, Iris C., additional, Tabbò, Fabrizio, additional, La Vecchia, Sofia, additional, Akman, Muhlis, additional, Napoli, Francesca, additional, Bungaro, Maristella, additional, Benso, Federica, additional, Aldieri, Elisabetta, additional, Bironzo, Paolo, additional, Kopecka, Joanna, additional, Passiglia, Francesco, additional, Righi, Luisella, additional, Novello, Silvia, additional, Scagliotti, Giorgio V., additional, and Riganti, Chiara, additional

Published
2023
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10. Contributors

Author

Aranda, Enrique, primary, Azizi, Fereidoun, additional, Bahadoran, Zahra, additional, Baritaki, Stavroula, additional, Barresi, Elisabetta, additional, Bonavida, Benjamin, additional, Bucolo, Claudio, additional, Calderone, Vincenzo, additional, Chegaev, Konstantin, additional, Chlopicki, Stefan, additional, Ciccone, Valerio, additional, Citi, Valentina, additional, Clementi, Emilio, additional, Da Settimo, Federico, additional, da Silva, Rafaella C., additional, Donadelli, Massimo, additional, Donnini, Sandra, additional, Drago, Filippo, additional, Dulak, Józef, additional, Durán, Nelson, additional, Durante, Miriam, additional, Ekmekcioglu, Suhendan, additional, Faienza, Fiorella, additional, Fávaro, Wagner J., additional, Ferraz, Letícia, additional, Filomeni, Giuseppe, additional, Forte, Elena, additional, Frosini, Maria, additional, Fusi, Fabio, additional, Gazzano, Elena, additional, Ghasemi, Asghar, additional, Gheibi, Sevda, additional, Gholami, Hanieh, additional, Giglio, Paola, additional, Giuffrè, Alessandro, additional, Grimm, Elizabeth A., additional, Jeddi, Sajad, additional, Kashfi, Khosrow, additional, Kim, Sun-Hee, additional, Kim, Won Jong, additional, Kopecka, Joanna, additional, Lazzeri, Luca, additional, Leggio, Gian Marco, additional, Malagrinò, Francesca, additional, Martelli, Alma, additional, Mascolo, Ludovica, additional, Mastronicola, Daniela, additional, Mirmiran, Parvin, additional, Monteiro, Hugo P., additional, Morbidelli, Lucia, additional, Myant, Kevin, additional, Nandi, Dipankar, additional, Ogata, Dai, additional, Pagnotta, Eleonora, additional, Papapetropoulos, Andreas, additional, Park, Dongsik, additional, Pathak, Sanmoy, additional, Pelegrino, Milena T., additional, Peñarando, Jon, additional, Perrotta, Cristiana, additional, Luzia Pinto, Moisés, additional, Vieira Pinto, Rosana, additional, Piragine, Eugenia, additional, Pittalà, Valeria, additional, Platania, Chiara Bianca Maria, additional, Reis, Adriana K.C.A., additional, Riganti, Chiara, additional, Rizza, Salvatore, additional, Rodrigue, Tiago, additional, Rodriguez-Ariza, Antonio, additional, Rolando, Barbara, additional, Roszik, Jason, additional, Rubinstein, Menachem, additional, Salaroglio, Iris C., additional, Salomone, Salvatore, additional, Saponara, Simona, additional, Saravanakumar, Gurusamy, additional, Scicinski, Jan, additional, Seabra, Amedea B., additional, Stern, Arnold, additional, Supuran, Claudiu T., additional, Taliani, Sabrina, additional, Testai, Lara, additional, Ugolini, Luisa, additional, Vannini, Federica, additional, Varchi, Greta, additional, Venturelli, Massimo, additional, Verma, Taru, additional, Vicente, João B., additional, Yadav, Shikha, additional, Ziche, Marina, additional, and Zuhra, Karim, additional

Published
2019
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12. Data from Mitochondria-Targeted Doxorubicin: A New Therapeutic Strategy against Doxorubicin-Resistant Osteosarcoma

Author

Buondonno, Ilaria, primary, Gazzano, Elena, primary, Jean, Sae Rin, primary, Audrito, Valentina, primary, Kopecka, Joanna, primary, Fanelli, Marilù, primary, Salaroglio, Iris C., primary, Costamagna, Costanzo, primary, Roato, Ilaria, primary, Mungo, Eleonora, primary, Hattinger, Claudia M., primary, Deaglio, Silvia, primary, Kelley, Shana O., primary, Serra, Massimo, primary, and Riganti, Chiara, primary

Published
2023
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13. Supplementary materials from Mitochondria-Targeted Doxorubicin: A New Therapeutic Strategy against Doxorubicin-Resistant Osteosarcoma

Author

Buondonno, Ilaria, primary, Gazzano, Elena, primary, Jean, Sae Rin, primary, Audrito, Valentina, primary, Kopecka, Joanna, primary, Fanelli, Marilù, primary, Salaroglio, Iris C., primary, Costamagna, Costanzo, primary, Roato, Ilaria, primary, Mungo, Eleonora, primary, Hattinger, Claudia M., primary, Deaglio, Silvia, primary, Kelley, Shana O., primary, Serra, Massimo, primary, and Riganti, Chiara, primary

Published
2023
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14. Supplementary Figure S7 from Mitochondria-Targeted Doxorubicin: A New Therapeutic Strategy against Doxorubicin-Resistant Osteosarcoma

Author

Buondonno, Ilaria, primary, Gazzano, Elena, primary, Jean, Sae Rin, primary, Audrito, Valentina, primary, Kopecka, Joanna, primary, Fanelli, Marilù, primary, Salaroglio, Iris C., primary, Costamagna, Costanzo, primary, Roato, Ilaria, primary, Mungo, Eleonora, primary, Hattinger, Claudia M., primary, Deaglio, Silvia, primary, Kelley, Shana O., primary, Serra, Massimo, primary, and Riganti, Chiara, primary

Published
2023
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21. Autocrine 17-β-estradiol/estrogen receptor-α loop determines the response to immune-checkpoint inhibitors in non-small cell lung cancer

Author

Anobile, Dario P, Salaroglio, Iris C, Tabbò, Fabrizio, La Vecchia, Sofia, Akman, Muhlis, Napoli, Francesca, Bungaro, Maristella, Benso, Federica, Aldieri, Elisabetta, Bironzo, Paolo, Kopecka, Joanna, Passiglia, Francesco, Righi, Luisella, Novello, Silvia, Scagliotti, Giorgio V, and Riganti, Chiara

Subjects
gender medicine, estrogen receptor α, non-small cell lung cancer, immunotherapy, 75 programmed death ligand 1
Published
2023

22. Abstract 2163: Gender and estrogens as key factors in the response to immunotherapy in non small cell lung cancer

Author

La Vecchia, Sofia, primary, Anobile, Dario Pasquale, additional, Tabbò, Fabrizio, additional, Salaroglio, Iris C., additional, Kopecka, Joanna, additional, Primo, Luca, additional, Righi, Luisella, additional, Scagliotti, Giorgio Vittorio, additional, Novello, Silvia, additional, Corbet, Cyril, additional, and Riganti, Chiara, additional

Published
2022
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23. Mitochondrial ROS drive resistance to chemotherapy and immune killing in hypoxic non-small cell lung cancer

Author

Salaroglio, Iris C., primary, Belisario, Dimas Carolina, additional, Akman, Muhlis, additional, Vecchia, Sofia La, additional, Godel, Martina, additional, Anobile, Dario Pasquale, additional, Ortone, Giacomo, additional, Digiovanni, Sabrina, additional, Fontana, Simona, additional, Costamagna, Costanzo, additional, Rubinstein, Menachem, additional, Kopecka, Joanna, additional, and Riganti, Chiara, additional

Published
2022
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24. C/EBP-β LAP regulates chemo-immuno-resistance in hypoxic non-small cell lung cancer

Author

Riganti, Chiara, primary, Salaroglio, Iris C., additional, Belisario, Dimas Carolina, additional, Akman, Muhlis, additional, Vecchia, Sofia La, additional, Godel, Martina, additional, Anobile, Dario Pasquale, additional, Ortone, Giacomo, additional, Digiovanni, Sabrina, additional, Fontana, Simona, additional, Costamagna, Costanzo, additional, and Kopecka, Joanna, additional

Published
2022
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25. C/EBP-β LAP regulates chemo-immuno-resistance in hypoxic non-small cell lung cancer

Author

Salaroglio, Iris C., primary, Belisario, Dimas Carolina, additional, Akman, Muhlis, additional, Vecchia, Sofia La, additional, Godel, Martina, additional, Anobile, Dario Pasquale, additional, Ortone, Giacomo, additional, Digiovanni, Sabrina, additional, Fontana, Simona, additional, Costamagna, Costanzo, additional, Kopecka, Joanna, additional, and Riganti, Chiara, additional

Published
2022
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27. Hypoxia as a driver of resistance to immunotherapy

Author

Associazione Italiana per la Ricerca sul Cancro, Foundation for Science and Technology, Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Kopecka, Joanna, Salaroglio, Iris C., Pérez-Ruiz, Elisabeth, Sarmento-Ribeiro, Ana Bela, Saponara, Simona, De Las Rivas, Javier, Riganti, Chiara, Associazione Italiana per la Ricerca sul Cancro, Foundation for Science and Technology, Instituto de Salud Carlos III, Ministerio de Sanidad (España), European Commission, Kopecka, Joanna, Salaroglio, Iris C., Pérez-Ruiz, Elisabeth, Sarmento-Ribeiro, Ana Bela, Saponara, Simona, De Las Rivas, Javier, and Riganti, Chiara

Abstract

Hypoxia, a hallmark of solid tumors, determines the selection of invasive and aggressive malignant clones displaying resistance to radiotherapy, conventional chemotherapy or targeted therapy. The recent introduction of immunotherapy, based on immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cells, has markedly transformed the prognosis in some tumors but also revealed the existence of intrinsic or acquired drug resistance. In the current review we highlight hypoxia as a culprit of immunotherapy failure. Indeed, multiple metabolic cross talks between tumor and stromal cells determine the prevalence of immunosuppressive populations within the hypoxic tumor microenvironment and confer upon tumor cells resistance to ICPIs and CAR T-cells. Notably, hypoxia-triggered angiogenesis causes immunosuppression, adding another piece to the puzzle of hypoxia-induced immunoresistance. If these factors concurrently contribute to the resistance to immunotherapy, they also unveil an unexpected Achille’s heel of hypoxic tumors, providing the basis for innovative combination therapies that may rescue the efficacy of ICPIs and CAR T-cells. Although these treatments reveal both a bright side and a dark side in terms of efficacy and safety in clinical trials, they represent the future solution to enhance the efficacy of immunotherapy against hypoxic and therapy-resistant solid tumors.

Published
2021

30. Wnt/IL‐1β/IL‐8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5

Author

Milosevic, Vladan, primary, Kopecka, Joanna, additional, Salaroglio, Iris C., additional, Libener, Roberta, additional, Napoli, Francesca, additional, Izzo, Stefania, additional, Orecchia, Sara, additional, Ananthanarayanan, Preeta, additional, Bironzo, Paolo, additional, Grosso, Federica, additional, Tabbò, Fabrizio, additional, Comunanza, Valentina, additional, Alexa‐Stratulat, Teodora, additional, Bussolino, Federico, additional, Righi, Luisella, additional, Novello, Silvia, additional, Scagliotti, Giorgio V., additional, and Riganti, Chiara, additional

Published
2019
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32. Design, Biological Evaluation, and Molecular Modeling of Tetrahydroisoquinoline Derivatives: Discovery of A Potent P-Glycoprotein Ligand Overcoming Multidrug Resistance in Cancer Stem Cells

Author

Riganti, Chiara, primary, Contino, Marialessandra, additional, Guglielmo, Stefano, additional, Perrone, Maria G., additional, Salaroglio, Iris C., additional, Milosevic, Vladan, additional, Giampietro, Roberta, additional, Leonetti, Francesco, additional, Rolando, Barbara, additional, Lazzarato, Loretta, additional, Colabufo, Nicola A., additional, and Fruttero, Roberta, additional

Published
2018
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34. Wnt/IL‐1β/IL‐8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.

Author

Milosevic, Vladan, Kopecka, Joanna, Salaroglio, Iris C., Libener, Roberta, Napoli, Francesca, Izzo, Stefania, Orecchia, Sara, Ananthanarayanan, Preeta, Bironzo, Paolo, Grosso, Federica, Tabbò, Fabrizio, Comunanza, Valentina, Alexa‐Stratulat, Teodora, Bussolino, Federico, Righi, Luisella, Novello, Silvia, Scagliotti, Giorgio V., and Riganti, Chiara

Subjects
ATP-binding cassette transporters, GENE expression profiling, OTOTOXICITY
Abstract

Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM‐initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness‐related pathways determine chemoresistance. Moreover, there are no predictive markers of IC‐associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness‐related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo‐sensitivity profile of IC and differentiated/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed. ABCB5‐knocked‐out (KO) IC clones were resensitized to the drugs in vitro and in patient‐derived xenografts. ABCB5 was transcriptionally activated by the Wnt/GSK3β/β‐catenin/c‐myc axis that also increased IL‐8 and IL‐1β production. IL‐8 and IL‐1β‐KO IC clones reduced the c‐myc‐driven transcription of ABCB5 and reacquired chemosensitivity. ABCB5‐KO clones had lower IL‐8 and IL‐1β secretion, and c‐myc transcriptional activity, suggesting that either Wnt/GSK3β/β‐catenin and IL‐8/IL‐1β signaling drive c‐myc‐mediated transcription of ABCB5. ABCB5 correlated with lower time‐to‐progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first‐line chemotherapy in MPM patients. What's new? The molecular mechanisms behind chemoresistance in malignant pleural mesothelioma (MPM) remain unclear. Nonetheless, tumor initiating cells (IC) and classical stemness factors, which serve major roles in tumor renewal and recurrence, are strongly implicated in MPM chemoresistance. Here, the ATP binding cassette transporter ABCB5, a known mediator of drug efflux, was identified as a key determinant of chemoresistance in ICs of primary mesotheliomas and as a negative prognostic factor in patients. ABCB5 expression was controlled by Wnt/IL‐1β/IL‐8/β‐catenin/c‐myc‐driven autocrine loops in IC. Disruption of these loops improved IC sensitivity to first‐line chemotherapy, suggesting that ABCB5 is a relevant therapeutic target in MPM. [ABSTRACT FROM AUTHOR]

Published
2020
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35. Loss of C/EBP-β LIP drives cisplatin resistance in malignant pleural mesothelioma

Author

Kopecka, Joanna, primary, Salaroglio, Iris C., additional, Righi, Luisella, additional, Libener, Roberta, additional, Orecchia, Sara, additional, Grosso, Federica, additional, Milosevic, Vladan, additional, Ananthanarayanan, Preeta, additional, Ricci, Luisa, additional, Capelletto, Enrica, additional, Pradotto, Monica, additional, Napoli, Francesca, additional, Di Maio, Massimo, additional, Novello, Silvia, additional, Rubinstein, Menachem, additional, Scagliotti, Giorgio V., additional, and Riganti, Chiara, additional

Published
2018
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39. Mitochondria-Targeted Doxorubicin: A New Therapeutic Strategy against Doxorubicin-Resistant Osteosarcoma

Author

Buondonno, Ilaria, primary, Gazzano, Elena, additional, Jean, Sae Rin, additional, Audrito, Valentina, additional, Kopecka, Joanna, additional, Fanelli, Marilù, additional, Salaroglio, Iris C., additional, Costamagna, Costanzo, additional, Roato, Ilaria, additional, Mungo, Eleonora, additional, Hattinger, Claudia M., additional, Deaglio, Silvia, additional, Kelley, Shana O., additional, Serra, Massimo, additional, and Riganti, Chiara, additional

Published
2016
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40. Temozolomide down-regulates P-glycoprotein in human blood–brain barrier cells by disrupting Wnt3 signaling

Author

Riganti, Chiara, primary, Salaroglio, Iris C., additional, Pinzòn-Daza, Martha L., additional, Caldera, Valentina, additional, Campia, Ivana, additional, Kopecka, Joanna, additional, Mellai, Marta, additional, Annovazzi, Laura, additional, Couraud, Pierre-Olivier, additional, Bosia, Amalia, additional, Ghigo, Dario, additional, and Schiffer, Davide, additional

Published
2013
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