Garaud, S. | bioRxiv Science

bioRxiv2024

B-Cell Involvement in Immune Checkpoint Inhibitor-Induced Lichen Planus: A Comparative Analysis with Non-Drug-Related Lichen Planus.

BackgroundImmune checkpoint inhibitors (ICI) have significantly improved cancer prognosis but can lead to immune-related adverse events (irAE), including cutaneous manifestations affecting 30% to 60% of ICI-treated patients. However, the physiopathology of cutaneaous irAE remains unclear. ObjectiveThis study investigated the immune infiltration in tissues affected by cutaneous irAE to elucidate their contribution to the pathogenesis of these toxicities. MethodsSkin biopsies from 6 patients with ICI-induced lichenoid eruptions were compared using imaging mass cytometry to samples from 7 controls with non-drug-related lichen planus. ResultsT cells were the predominant cell type within the inflammatory infiltrate in all samples, but we observed a reduced T-cell infiltration and an increased B-cell frequency in ICI-induced lichen planus compared to non-drug related lichen planus. Among B cells, we observed a significant decrease in IgD-CD27-double-negative B cells and an increase in IgD+CD27-naive B cells. Spatial analysis demonstrated that infiltrating B cells were organized in aggregates close to T cells in ICI-induced lichen planus. LimitationsThis is a retrospective single-center study with a relatively small sample size. ConclusionThis study sheds light on the involvement of B cells in the pathogenesis of ICI-induced lichen planus, suggesting distinct immunological mechanisms from non-drug-related lichen planus. CAPSULE SUMMARYO_LILichenoid manifestations are a common but understudied side effect occurring in patients receiving anti-PD-1 antibodies. C_LIO_LIICI-induced lichen planus displays distinct physiopathology from non-drug-related lichen planus, with a decrease of T-cell infiltration concomitantly to the increase of B cells organized in aggregates. C_LI

immunology↗

bioRxiv2022

Deciphering the maturation of tertiary lymphoid structures in cancer and inflammatory diseases of the digestive tract using imaging mass cytometry: from high-level data to a simple architectural and functional grading

ObjectivePersistent inflammation can promote the development of tertiary lymphoid structures (TLS) within tissues resembling the secondary lymphoid organs (SLO) as lymph nodes (LN). The composition of the TLS across different organs and diseases could be of pathophysiological and medical interest. In this work, we compared TLS to SLO and between cancer and inflammatory diseases of the digestive tract. DesignColorectal and gastric tissues with different inflammatory diseases and cancers from the department of pathology of CHU Brest were analyzed based on 39 markers using imaging mass cytometry (IMC). Unsupervised and supervised clustering analyses of IMC images were used to compare SLO and TLS. ResultsUnsupervised analyses tended to group TLS per patient but not per disease. Supervised analyses of IMC images revealed that LN had a more organized structure than TLS and non-encapsulated SLO Peyers patches. TLS followed a maturation spectrum with close correlations between germinal cell (GC) markers evolution. The correlations between organizational and functional markers made relevant the previously proposed TLS division into three stages: lymphoid-aggregates (LA) (CD20+CD21-CD23-) had neither organization nor GC functionality, non-GC TLS (CD20+CD21+CD23-) were organized but lacked GCs functionality and GC-like TLS (CD20+CD21+CD23+) had GCs organization and functionality. This architectural and functional maturation grading of TLS pointed to differences across diseases. ConclusionTLS architectural and functional maturation grading is accessible with few markers allowing future diagnostic, prognostic, and predictive studies on the value of TLS grading, quantification and location within pathological tissues in cancers and inflammatory diseases. KEY MESSAGES- What is already known on this topic: Tertiary lymphoid structures (TLS) arise in organs under various pathological conditions and can be of prognostic significance. - What this study adds: This study deciphers the composition of TLS in digestive cancers and inflammatory diseases using massively multiplexed (39 markers) imaging mass cytometry (IMC). Beyond the term TLS, this study points to the heterogeneity of these structures in terms of composition and maturation but also the relevance of a simple architectural and functional three-stage grading of TLS. - How this study might affect research, practice, or policy: This preliminary study paves the way for future studies evaluating the diagnostic, prognostic and theranostic values of TLS maturation grading, quantification and location within tissues as novel biomarkers in inflammatory diseases and cancers.

immunology↗