OncoImmunology (Dec 2025)

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

  • 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

DOI
https://doi.org/10.1080/2162402X.2025.2513109
Journal volume & issue
Vol. 14, no. 1

Abstract

Read online

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.

Keywords