Abstract
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(-/low)CD27(+)) 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(+)CD20(low)CD25(low)CD27(low) 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.