Biology subjects

Lamant, L.

Publications and source records attributed to Lamant, L..

4 recordsLinked to original sources

bioRxiv2026

Tumor microenvironment signature associated with morphology in systemic ALK-positive anaplastic large cell lymphoma

Peripheral T-cell lymphomas (PTCL) are heterogeneous entities whose tumoral microenvironment (TME) may influence disease phenotype and outcome. To dissect their immune and stromal composition, we used two complementary algorithms, CIBERSORTx and MCP-counter, on Affymetrix data from 255 patients whole-tissue biopsies, including 78 systemic anaplastic large cell lymphomas (ALCL). Clustering based on inferred cell proportions revealed a clear separation between ALCL and other PTCL subtypes, including angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS). ALCL-enriched clusters were characterised by granulocytes and macrophages lineages, mast cells, NK cells, memory CD4+ T-cells, as well as fibroblast and endothelial signatures, whereas as expected, AITL cluster was enriched for T-follicular helper cells, B-cells and macrophages. Finally, we focused on 66 ALCL cases with relapse risk and morphological subtype clinical annotations. Distinct TME features enriched in M1 macrophages and monocytes were associated with adverse outcomes and non-common morphological variants. Transcriptomic analyses of mononuclear phagocytes across Affymetrix and RNAseq datasets confirmed distinct clustering according to cell morphology. These analyses identified potential biomarkers associated with uncommon variants and absent from ALK+ ALCL cell lines, confirming their TME origin. Macrophage- and monocyte-related signatures emerged as key contributors in ALK+ ALCL patients heterogeneity, linking TME patterns to tumor morphology and prognosis. These signatures may serve as biomarkers for patient risk stratification and guide the development of targeted therapies.

cancer biology↗

bioRxiv2026

CircZBTB46, a promising therapeutic target in crizotinib resistant ALK-positive T lymphomas

Circular RNAs (circRNAs) are increasingly recognized as functional non-coding transcripts with oncogenic potential. Here, a comprehensive analysis of circRNA expression in primary ALK(+) anaplastic large-cell lymphoma (ALK(+) ALCL) is presented. Integrated transcriptomic profiling revealed that aberrant expression of circZBTB46 and of its linear host transcript, normally restricted to dendritic cells, is exclusive to ALK(+) lymphoma cells and driven by the oncogenic NPM1-ALK/STAT3 axis. Functional studies showed that circZBTB46, unlike its protein-coding counterpart, promotes resistance to the ALK inhibitor crizotinib. Silencing circZBTB46 restored crizotinib sensitivity in resistant ALCL cells both in vitro and in vivo. Transcriptomic analyses identified PIP5K1C as a downstream effector regulated through a competitive endogenous RNA mechanism in which circZBTB46 acts as a sponge to miR-25-3p, alleviating its repression of PIP5K1C. These findings uncover a previously unrecognized mechanism of drug resistance in ALK(+) ALCL and establish circZBTB46 as a promising therapeutic target.

cancer biology↗

bioRxiv2023

3-D deconvolution of human skin immune architecture with Multiplex Annotated Tissue Imaging System (MANTIS)

Routine clinical assays, such as conventional immunohistochemistry, often fail to resolve the regional heterogeneity of complex inflammatory skin conditions. Here we introduce MANTIS (Multiplexed Annotated Tissue Imaging System), a flexible analytic pipeline compatible with routine practice, specifically-designed for spatially-resolved immune phenotyping of the skin in experimental or clinical samples. Based on phenotype attribution matrices coupled to -shape algorithms, MANTIS projects a representative digital immune landscape, while enabling automated detection of major inflammatory clusters and concomitant single-cell data quantification of biomarkers. We observed that severe pathological lesions from systemic lupus erythematosus, Kawasaki syndrome or COVID-19-associated skin manifestations share common quantitative immune features, while displaying a non-random distribution of cells with the formation of disease-specific dermal immune structures. Given its accuracy and flexibility, MANTIS is designed to solve the spatial organization of complex immune environments to better apprehend the pathophysiology of skin manifestations.

immunology↗

bioRxiv2022

DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness

Aberrant DNA methylation is a well-known feature of tumours and has been associated with metastatic melanoma. However, since melanoma cells are highly heterogeneous, it has been challenging to use affected genes to predict tumour aggressiveness, metastatic evolution, and patients outcomes. We hypothesized that common aggressive hypermethylation signatures should emerge early in tumorigenesis and should be shared in aggressive cells, independent of the physiological context under which this trait arises. We compared paired melanoma cell lines with the following properties: (i) each pair comprises one aggressive counterpart and its parental cell line, and (ii) the aggressive cell lines were each obtained from different host and their environment (human, rat, and mouse), though starting from the same parent cell line. Next, we developed a multi-step genomic pipeline that combines the DNA methylome profile with a chromosome cluster-oriented analysis. A total of 229 differentially hypermethylated genes were commonly found in the aggressive cell lines. Genome localization analysis revealed hypermethylation peaks and clusters, identifying eight hypermethylated gene promoters for validation in tissues from melanoma patients. Five CpG identified in primary melanoma tissues were transformed into a DNA methylation score that can predict survival (Log-rank test, p=0.0008). This strategy is potentially universally applicable to other diseases involving DNA methylation alterations.

cancer biology↗