Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)

Perioperative 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...

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Main Authors: Belén Sierra Rodero, Cristina Martínez-Toledo, Ernest Nadal, Marta Molina-Alejandre, Rosario García Campelo, Ángeles Gil-González, Bartomeu Massuti, Aránzazu García-Grande, Manuel Dómine, Amelia Insa, Javier de Castro Carpeño, Gerardo Huidobro Vence, Margarita Majem, Alex Martinez-Marti, Diego Megias, Daniel Lobato, Ana Collazo-Lorduy, Virginia Calvo, Mariano Provencio, Alberto Cruz-Bermúdez
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2025.2513109
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author Belén Sierra Rodero
Cristina Martínez-Toledo
Ernest Nadal
Marta Molina-Alejandre
Rosario García Campelo
Ángeles Gil-González
Bartomeu Massuti
Aránzazu García-Grande
Manuel Dómine
Amelia Insa
Javier de Castro Carpeño
Gerardo Huidobro Vence
Margarita Majem
Alex Martinez-Marti
Diego Megias
Daniel Lobato
Ana Collazo-Lorduy
Virginia Calvo
Mariano Provencio
Alberto Cruz-Bermúdez
author_facet Belén Sierra Rodero
Cristina Martínez-Toledo
Ernest Nadal
Marta Molina-Alejandre
Rosario García Campelo
Ángeles Gil-González
Bartomeu Massuti
Aránzazu García-Grande
Manuel Dómine
Amelia Insa
Javier de Castro Carpeño
Gerardo Huidobro Vence
Margarita Majem
Alex Martinez-Marti
Diego Megias
Daniel Lobato
Ana Collazo-Lorduy
Virginia Calvo
Mariano Provencio
Alberto Cruz-Bermúdez
author_sort Belén Sierra Rodero
collection DOAJ
description Perioperative 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.
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spelling doaj-art-7db2ffc596d54ec7b5c705b0cd67d28a2025-08-20T02:32:07ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2513109Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)Belén Sierra Rodero0Cristina Martínez-Toledo1Ernest Nadal2Marta Molina-Alejandre3Rosario García Campelo4Ángeles Gil-González5Bartomeu Massuti6Aránzazu García-Grande7Manuel Dómine8Amelia Insa9Javier de Castro Carpeño10Gerardo Huidobro Vence11Margarita Majem12Alex Martinez-Marti13Diego Megias14Daniel Lobato15Ana Collazo-Lorduy16Virginia Calvo17Mariano Provencio18Alberto Cruz-Bermúdez19Servicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainServicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainInstitut Català d’Oncologia (ICO), Oncobell Program, IDIBELL. L’Hospitalet De Llobregat, Barcelona, SpainServicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainServicio de Oncología Médica, Hospital Universitario A Coruña, A Coruña, A Coruña, SpainServicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainServicio de Oncología Médica, Hospital General Dr. Balmis de Alicante, ISABIAL, Alicante, SpainFlow Cytometry Core Facility, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Madrid, SpainServicio de Oncologia Médica, Hospital Universitario Fundación Jiménez Díaz, Madrid, SpainFundación INCLIVA, Servicio de Oncología Médica, Hospital Clínico Universitario de Valencia, Valencia, SpainServicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain, Servicio de Oncología Médica, Hospital Alvaro Cunqueiro, Complexo Hospitalario Universitario de Vigo, SpainServicio de Oncología Médica, Hospital de la Santa Creu i Sant Pau, Barcelona, SpainVall Hebron Institute of Oncology (VHIO), Servicio de Oncología Médica, Hospital Universitari Vall d’Hebrón, Barcelona, SpainUnidad de Microscopía Óptica Avanzada, Instituto de Salud Carlos III, Majadahonda, SpainServicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainServicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainServicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainServicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainServicio de Oncología Médica, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, SpainPerioperative 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.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2513109B lymphocyteschemoimmunotherapyflow cytometryNSCLCperioperative
spellingShingle Belén Sierra Rodero
Cristina Martínez-Toledo
Ernest Nadal
Marta Molina-Alejandre
Rosario García Campelo
Ángeles Gil-González
Bartomeu Massuti
Aránzazu García-Grande
Manuel Dómine
Amelia Insa
Javier de Castro Carpeño
Gerardo Huidobro Vence
Margarita Majem
Alex Martinez-Marti
Diego Megias
Daniel Lobato
Ana Collazo-Lorduy
Virginia Calvo
Mariano Provencio
Alberto Cruz-Bermúdez
Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)
OncoImmunology
B lymphocytes
chemoimmunotherapy
flow cytometry
NSCLC
perioperative
title Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)
title_full Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)
title_fullStr Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)
title_full_unstemmed Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)
title_short Peripheral memory B cell population maintenance and long-term survival after perioperative chemoimmunotherapy in NSCLC (NADIM trial)
title_sort peripheral memory b cell population maintenance and long term survival after perioperative chemoimmunotherapy in nsclc nadim trial
topic B lymphocytes
chemoimmunotherapy
flow cytometry
NSCLC
perioperative
url https://www.tandfonline.com/doi/10.1080/2162402X.2025.2513109
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