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                  <mods:namePart>Sierra-Rodero, Belen</mods:namePart>
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                  <mods:namePart>Martínez-Toledo, Cristina</mods:namePart>
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                  <mods:namePart>Molina-Alejandre, Marta</mods:namePart>
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                  <mods:namePart>Gil-González, Ángeles</mods:namePart>
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               <mods:name>
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                  <mods:namePart>Nadal, Ernest</mods:namePart>
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                  <mods:namePart>Garcia Campelo, Rosario</mods:namePart>
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                     <mods:roleTerm type="text">author</mods:roleTerm>
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                  <mods:namePart>MARTINEZ-MARTI, ALEX</mods:namePart>
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                  <mods:dateIssued encoding="iso8601">2025-08-11T06:35:46Z2025-08-11T06:35:46Z2025</mods:dateIssued>
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               <mods:abstract>B lymphocytes; Chemoimmunotherapy; Flow cytometryLinfocitos B; Quimioinmunoterapia; Citometría de flujoLimfòcits B; Quimioimmunoteràpia; Citometria de fluxPerioperative chemoimmunotherapy has significantly improved survival rates for non-small cell lung cancer (NSCLC). However, current tissue biomarkers remain inadequate, underscoring the need for more sensitive and accessible alternatives to monitor relapse risk. Intratumoral B-cells are increasingly recognized for their role in enhancing immunotherapy outcomes, yet the contribution of peripheral B-cells to immune surveillance remains unexplored. Peripheral B-cell immunophenotypes were analyzed from blood samples (at diagnosis, post-neoadjuvant, and at 6- and 12-months of adjuvant treatment) in 41 stage IIIA NSCLC patients treated with perioperative nivolumab plus chemotherapy, included in the NADIM clinical trial (NCT03081689). Results were correlated with 5-year survival outcomes and validated through unsupervised clustering. An increase in the percentage of total B-cells (CD19+CD20+) and naïve B-cells (CD19+CD20+CD24+CD38+CD27-CD10-), along with a reduction in CD20 expression on total B-cells, a decrease in the proportion of memory B-cells (CD19+CD20+CD24+CD38-/lowCD27+) and transitional B-cells (CD19+CD20+CD24++CD38++CD10+), was observed during the time encompassed between the end of neoadjuvant treatment and the posterior 6 months of adjuvant treatment. Higher levels of CD20 expression on total B-cells, along with an increased percentage of memory B-cells, or activated B-cells (CD19+CD20+CD25+), at 6- and 12-months of adjuvant treatment, were associated with increased survival. Conversely, higher levels of a newly described circulating population of CD19+CD20lowCD25lowCD27low B-cells during adjuvant treatment were linked to disease progression. Perioperative nivolumab plus chemotherapy in resectable NSCLC patients induces significant changes in peripheral B-cells. The persistence of circulating memory B-cells during adjuvant treatment might play a crucial role in survival.Work in the authors’ laboratories was supported by “Instituto de Salud Carlos III” (ISCIII) PI19/01652 and PI22/01223 grants cofounded by European Regional Development Fund (ERDF), Bristol-Myers Squibb (BMS), Ministry of Science and Innovation RTC2017-6502-1 ‘INmunoSIGHT’, RTC2019-007359-1 ‘BLI-O’, CPP2022-009545 ‘STRAGEN-IO’, and European Union’s Horizon 2020 research and innovation programme, CLARIFY 875160 grant, to MP. AC-B is supported by a “Miguel Servet” contract CP23/00044 by ISCIII and received an ISCIII project grant PI23/01054 both cofounded by European Union. CM-T is supported by Comunidad de Madrid PIPF-2022/SAL-GL-25283 contract granted to MP. MM-A is supported by Ayuda Predoctoral Asociación Española Contra el Cáncer (AECC) Madrid 2023 contract granted to MP. AnG-G was supported by Comunidad de Madrid and European social fund PEJ-2023-AI/SAL-GL-27634 contract, and now is supported by FI24/00270 predoctoral contract from ISCIII granted to AC-B.</mods:abstract>
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               <mods:accessCondition type="useAndReproduction">Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess</mods:accessCondition>
               <mods:subject>
                  <mods:topic>Quimioteràpia combinada</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Pulmons - Càncer - Tractament</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Cèl·lules B</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Other subheadings::Other subheadings::Other subheadings::/drug therapy</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>ANATOMY::Cells::Antibody-Producing Cells::B-Lymphocytes</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>ANATOMÍA::células::células productoras de anticuerpos::linfocitos B</mods:topic>
               </mods:subject>
               <mods:titleInfo>
                  <mods:title>Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)</mods:title>
               </mods:titleInfo>
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