Single‐cell transcriptome sequencing of B‐cell heterogeneity and tertiary lymphoid structure predicts breast cancer prognosis and neoadjuvant therapy efficacy

Abstract

BackgroundBreast cancer (BC) is a highly heterogeneous disease, and although immunotherapy has recently increased patient survival in a number of solid and hematologic malignancies, most BC subtypes respond poorly to immune checkpoint blockade therapy (ICB). B cells, particularly those that congregate in tertiary lymphoid structures (TLS), play a significant role in antitumour immunity. However, B‐cell heterogeneity at single‐cell resolution and its clinical significance with TLS in BC need to be explored further.MethodsPrimary tumour lesions and surrounding normal tissues were taken from 14 BC patients, totaling 124,587 cells, for single‐cell transcriptome sequencing and bioinformatics analysis.ResultsBased on the usual markers, the single‐cell transcriptome profiles were classified into various clusters. A thorough single‐cell study was conducted with a focus on tumour‐infiltrating B cells (TIL‐B) and tumour‐associated neutrophils (TAN). TIL‐B was divided into five clusters, and unusual cell types, such as follicular B cells, which are strongly related to immunotherapy efficacy, were identified. In BC, TAN and TIL‐B infiltration are positively correlated, and at the same time, compared with TLS‐high, TAN and TIL‐B in TLS‐low group are significantly positively correlated.ConclusionsIn conclusion, our study highlights the heterogeneity of B cells in BC, explains how B cells and TLS contribute significantly to antitumour immunity at both the single‐cell and clinical level, and offers a straightforward marker for TLS called CD23. These results will offer more pertinent information on the applicability and effectiveness of tumour immunotherapy for BC.

Heterogeneity of Cervical Cancer-Associated Tertiary Lymphoid Structures (TLSs) and Their Specific Interrelation With Clinicopathological Parameters

“…The structural, molecular, and topographical heterogeneity of TLS has been demonstrated in other types of malignancies, such as renal cancer [ 20 ], breast cancer [ 21 ], and oral cancer [ 22 ]. The majority of lesions in this study were squamous cell carcinomas.…”

Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer

“…However, it remains an open question whether the predictive value of TLS is exclusive to ICIs or extends to predicting sensitivity to neoTx, particularly in LARC patients. In breast cancer, four studies have demonstrated a significant association between TLS and the efficacy of neoadjuvant chemotherapy 31 – 34 . In the NT cohort, TLS was observed in 98.3% of cases.…”

Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications

“… 119 Using single‐cell transcriptome sequencing, Wang et al. 120 identified CD23 as a biomarker of TLS in BC and proposed that heterogeneity of B cells in TLS determines the efficacy of immunotherapy. DC heterogeneity has also been of concern, and investigators determined that the functional status of CCL19‐expressing DCs correlated with favorable anti‐PD1 responses, T‐cell immunity, and the presence of TLS.…”