Functionally impaired follicular helper T cells induce regulatory B cells and CD14⁺ human leukocyte antigen‐DR⁻ cell differentiation in non‐small cell lung cancer

Abstract

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 CD14+ 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.

Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state

“…One study suggested that circulating follicular helper T cells are higher in advanced stage NSCLC 38 . Another 2 studies showed that circulating Th1 cells are higher in early stage NSCLC, but circulating Th2 cells are higher in advanced stage NSCLC 39,40 . However, how tumor stage affects Th cells in the TME needs further investigation.…”

Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung carcinoma

“…Second, in different stages of NSCLC, the change of Tfh subtypes is inconsistent. The Tfh1 cell abundance in stage II-IV decreased, while Tfh2 and Tfh17 abundances in stage II-IV increased (Qiu et al, 2018) and the ratio of Tfh1, Tfh2, and Tfh17 abundances might lead to the Tfh cell infiltration abundance changing. Further, benefit from immune escape, tumor cells can migrate to other space.…”

Transcriptional Profiles of Long Non-coding RNA and mRNA in Sheep Mammary Gland During Lactation Period

“…A sharp increase (from PP to EL) followed by a slight decrease (from EL to PL) during the three periods was detected in the expression level of apoptosis-related genes, such as DR1 and several members of the SLC family ( SLC26A2 , SLC35C2 ). Given the critical role of these genes in the apoptosis of cells ( Morioka et al, 2018 ; Qiu et al, 2018 ; Scalise et al, 2018 ), we hypothesize that the decline in lactation may begin during PL in sheep. Furthermore, members of the CDK and CCN families ( Yeger and Perbal, 2016 ; Sarek et al, 2019 ) also showed non-significant up-regulation in PL vs EL, which also is consistent with our hypothesis.…”