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8 results on '"Baraibar, Iosune"'

5. A Comprehensive Biomarker Analysis of Microsatellite Unstable/Mismatch Repair Deficient Colorectal Cancer Cohort Treated with Immunotherapy

Author

Élez, Elena, primary, Mulet-Margalef, Núria, additional, Sanso, Miriam, additional, Ruiz-Pace, Fiorella, additional, Mancuso, Francesco M., additional, Comas, Raquel, additional, Ros, Javier, additional, Argilés, Guillem, additional, Martini, Giulia, additional, Sanz-Garcia, Enrique, additional, Baraibar, Iosune, additional, Salvà, Francesc, additional, Noguerido, Alba, additional, Cuadra-Urteaga, Jose Luis, additional, Fasani, Roberta, additional, Garcia, Ariadna, additional, Jimenez, Jose, additional, Aguilar, Susana, additional, Landolfi, Stefania, additional, Hernández-Losa, Javier, additional, Braña, Irene, additional, Nuciforo, Paolo, additional, Dienstmann, Rodrigo, additional, Tabernero, Josep, additional, Salazar, Ramon, additional, and Vivancos, Ana, additional

Published
2022
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7. Id1 and PD-1 Combined Blockade Impairs Tumor Growth and Survival of KRAS-mutant Lung Cancer by Stimulating PD-L1 Expression and Tumor Infiltrating CD8+ T Cells

Author

Baraibar, Iosune, primary, Roman, Marta, additional, Rodríguez-Remírez, María, additional, López, Inés, additional, Vilalta, Anna, additional, Guruceaga, Elisabeth, additional, Ecay, Margarita, additional, Collantes, María, additional, Lozano, Teresa, additional, Alignani, Diego, additional, Puyalto, Ander, additional, Oliver, Ana, additional, Ortiz-Espinosa, Sergio, additional, Moreno, Haritz, additional, Torregrosa, María, additional, Rolfo, Christian, additional, Caglevic, Christian, additional, García-Ros, David, additional, Villalba-Esparza, María, additional, De Andrea, Carlos, additional, Vicent, Silvestre, additional, Pío, Rubén, additional, Lasarte, Juan José, additional, Calvo, Alfonso, additional, Ajona, Daniel, additional, and Gil-Bazo, Ignacio, additional

Published
2020
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8. A Comprehensive Biomarker Analysis of Microsatellite Unstable/Mismatch Repair Deficient Colorectal Cancer Cohort Treated with Immunotherapy

Author

Elena Élez, Núria Mulet-Margalef, Miriam Sanso, Fiorella Ruiz-Pace, Francesco M. Mancuso, Raquel Comas, Javier Ros, Guillem Argilés, Giulia Martini, Enrique Sanz-Garcia, Iosune Baraibar, Francesc Salvà, Alba Noguerido, Jose Luis Cuadra-Urteaga, Roberta Fasani, Ariadna Garcia, Jose Jimenez, Susana Aguilar, Stefania Landolfi, Javier Hernández-Losa, Irene Braña, Paolo Nuciforo, Rodrigo Dienstmann, Josep Tabernero, Ramon Salazar, Ana Vivancos, Élez, Elena, Mulet-Margalef, Núria, Sanso, Miriam, Ruiz-Pace, Fiorella, Mancuso, Francesco M, Comas, Raquel, Ros, Javier, Argilés, Guillem, Martini, Giulia, Sanz-Garcia, Enrique, Baraibar, Iosune, Salvà, Francesc, Noguerido, Alba, Cuadra-Urteaga, Jose Lui, Fasani, Roberta, Garcia, Ariadna, Jimenez, Jose, Aguilar, Susana, Landolfi, Stefania, Hernández-Losa, Javier, Braña, Irene, Nuciforo, Paolo, Dienstmann, Rodrigo, Tabernero, Josep, Salazar, Ramon, Vivancos, Ana, Institut Català de la Salut, [Élez E, Argilés G, Sanz-Garcia E, Baraibar I, Salvà F, Noguerido A, Garcia A, Tabernero J] Colorectal Cancer Program, Medical Oncology Department, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Mulet-Margalef N] Colorectal Cancer Program, Medical Oncology Department, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Colorectal Cancer Unit, Medical Oncology Department, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Barcelona, Spain. [Sanso M] Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Genomics for Precision Oncology Laboratory, Fundació Institut d’Investigació Sanitària Illes Balears (IdISBa), Palma de Mallorca, Spain. [Ruiz-Pace F, Comas R, Dienstmann R] Oncology Data Science Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Mancuso FM] Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Research and Development Department, Universal Diagnostics S.L., Sevilla, Spain. [Ros J, Martini G] Colorectal Cancer Program, Medical Oncology Department, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy. [Cuadra-Urteaga JL] Colorectal Cancer Program, Medical Oncology Department, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Medical Oncology, IOB—Hospital Quirón, Barcelona, Spain. [Fasani R, Jimenez J, Nuciforo P] Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Aguilar S] Molecular Prescreening Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Landolfi S, Hernández-Losa J] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Braña I] Medical Oncology Department, Research Unit for Molecular Therapy of Cancer, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Salazar R] Colorectal Cancer Unit, Medical Oncology Department, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Barcelona, Spain. Medical Oncology Department, Research Unit for Molecular Therapy of Cancer, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Vivancos A] Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Genetic Phenomena::Genetic Phenomena::Genomic Instability::Microsatellite Instability [PHENOMENA AND PROCESSES], Immunoteràpia, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], colorectal cancer, Immunotheraphy, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Catalysis, Inorganic Chemistry, Còlon - Càncer - Tractament, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], Càncer colorectal, Recte - Càncer - Tractament, Other subheadings::/therapeutic use [Other subheadings], MSI-H/dMMR, immunotherapy, biomarkers, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Satèl·lits (Genètica), Otros calificadores::/uso terapéutico [Otros calificadores], Biochemical markers, Organic Chemistry, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], fenómenos genéticos::fenómenos genéticos::inestabilidad genómica::inestabilidad de microsatélites [FENÓMENOS Y PROCESOS], General Medicine, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], Colorectal cancer, Computer Science Applications, Marcadors bioquímics, biomarker, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS]
Abstract

Biomarkers; Colorectal cancer; Immunotherapy Biomarcadors; Càncer colorectal; Immunoteràpia Biomarcadores; Cáncer colorrectal; Inmunoterapia The search for immunotherapy biomarkers in Microsatellite Instability High/Deficient Mismatch Repair system (MSI-H/dMMR) metastatic colorectal cancer (mCRC) is an unmet need. Sixteen patients with mCRC and MSI-H/dMMR (determined by either immunohistochemistry or polymerase chain reaction) treated with PD-1/PD-L1 inhibitors at our institution were included. According to whether the progression-free survival with PD-1/PD-L1 inhibitors was longer than 6 months or shorter, patients were clustered into the IT-responder group (n: 9 patients) or IT-resistant group (n: 7 patients), respectively. In order to evaluate determinants of benefit with PD-1/PD-L1 inhibitors, we performed multimodal analysis including genomics (through NGS panel tumour-only with 431 genes) and the immune microenvironment (using CD3, CD8, FOXP3 and PD-L1 antibodies). The following mutations were more frequent in IT-resistant compared with IT-responder groups: B2M (4/7 versus 2/9), CTNNB1 (2/7 versus 0/9), and biallelic PTEN (3/7 versus 1/9). Biallelic ARID1A mutations were found exclusively in the IT-responder group (4/9 patients). Tumour mutational burden did not correlate with immunotherapy benefit, neither the rate of indels in homopolymeric regions. Of note, biallelic ARID1A mutated tumours had the highest immune infiltration and PD-L1 scores, contrary to tumours with CTNNB1 mutation. Immune microenvironment analysis showed higher densities of different T cell subpopulations and PD-L1 expression in IT-responders. Misdiagnosis of MSI-H/dMMR inferred by discordances between immunohistochemistry and polymerase chain reaction was only found in the IT-resistant population (3/7 patients). Biallelic ARID1A mutations and Wnt signalling activation through CTNNB1 mutation were associated with high and low T cell immune infiltrates, respectively, and deserve special attention as determinants of response to PD-1/PD-L1 inhibitors. The non-MSI-H phenotype in dMMR is associated with poor benefit to immunotherapy. Our results suggest that mechanisms of resistance to immunotherapy are multi-factorial. This research was funded by Merck Research Grants (Call 2018) in the Area of Colorectal Cancer Clinical Investigation.

Published
2022
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