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Non‐small cell lung cancer ( NSCLC ) represents one of the most common and aggressive cancers worldwide, as it typically displays irreversible progression and poor prognosis. Interaction between programmed death 1 ( PD ‐1) and its ligand,  PD ‐L1, plays important roles in tumor immunology. Follicular helper T (Tfh) cells have characteristically high  PD ‐1 expression; thus, in the present study, we investigated the role of circulating Tfh cells and their correlation with disease‐free survival after tumor resection in  NSCLC . We found significantly higher number of Tfh cells but lower serum interleukin ( IL )‐21 levels in  NSCLC  patients, especially in those with advanced stage ( III  and  IV ), indicating that the function of Tfh cells to produce  IL ‐21 was impaired. Further analysis showed that the increase in Tfh cells was attributable to an expansion of the  PD ‐1 + ‐Tfh2 and  PD ‐1 + ‐Tfh17 subtypes. Functional analysis showed that Tfh cells from  NSCLC  patients induced the differentiation of regulatory B cells and  CD 14 +  human leukocyte antigen ( HLA )‐ DR  −  cells. Interestingly, the number of Tfh1 subtypes in  NSCLC  patients was negatively correlated with disease‐free survival after tumor resection. In short, the high number and abnormal function of Tfh cells could cause further immunosuppression and lead to tumor development in  NSCLC . Rescuing Tfh functions therefore represents a potential therapeutic strategy in  NSCLC .

cancer science

Functionally impaired follicular helper T cells induce regulatory B cells and  CD 14 +  human leukocyte antigen‐ DR  −  cell differentiation in non‐small cell lung cancer