Mots-Clés
scRNA-seq
cancer
spatial transcriptomics
Description
Titre du projet:
Deciphering the evolution of immune surveillance mechanisms through breast cancer progression.
Nom, adresse de l’unité d’accueil / Nom du responsable de l’unité :
Centre de recherche en cancérologie de Lyon
28 rue Laënnec, 69373 Lyon cedex 08, France
Directeur : Dr. Patrick MEHLEN
Nom, adresse de l’équipe d’accueil / Nom du responsable d’équipe :
Equipe CISTAR “Cancer Immune Surveillance and Therapeutic tARgeting”
Responsable d’équipe : Dr. Christophe CAUX
Nom, tel, adresse e-mail de l’encadrant de stage :
Léo Laoubi, PhD, leo.laoubi@lyon.unicancer.fr
Aurélien Voissière, PhD, aurelien.voissiere@lyon.unicancer.fr
Description du projet de stage :
Breast cancer (BC) and especially its most aggressive form the triple negative breast cancer (TNBC) represents a major public health issue. The early detection of BC is essential to start a therapeutic treatment as early as possible and improve the clinical outcome. More and more evidence indicate that even before the clinical detection of tumor lesions, the dialogue between immune cells and non-immune cells in normal tissue and preneoplastic lesions is critical for tumor control. Indeed, epithelial cells can undergo genetic, epigenetic alterations leading to their malignant profile and the appearance of tumor lesions. Thus, our objective is to evaluate the phenotype, the spatial distribution and cellular/molecular interactions between epithelial and immune cell populations in normal breast tissues (with or without genetic predisposition such as BRCA1 mutation), ductal carcinoma in situ (DCIS) and invasive tumors to identify early immune evasion mechanisms and propose innovative immune interception strategies. To do so, we will capitalize on public datasets of single cell (sc) RNA-seq and in-house generated spatial transcriptomics (ST) datasets (Xenium, 10X Genomics). The intern project will consist in integrating scRNA-seq (transcriptomics profiles, cluster identities, ligand-receptor inference) and ST (cell locations, cell-cell distance, niches) datasets to (i) map the evolution of spatial cell distribution through tumor progression and (ii) reveal cell-cell and ligand/receptor interactions taking place at each stage of breast cancer evolution.
Modèle et techniques utilisées :
- Datasets: Human scRNA-seq and spatial transcriptomics (Xenium 10X Genomics)
- Tools used: Seurat, Scanpy, Squidpy, Novae / Sopa, NicheNet / Cellchat, Slingshot / Cytotrace, Xenium Explorer (10x Genomics), R, Python.
Publications d’intérêt :
Reed, A.D., Pensa, S., Steif, A. et al. A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast. Nat Genet 56, 652–662 (2024). https://doi.org/10.1038/s41588-024-01688-9
Wu, S.Z., Al-Eryani, G., Roden, D.L. et al. A single-cell and spatially resolved atlas of human breast cancers. Nat Genet 53, 1334–1347 (2021). https://doi.org/10.1038/s41588-021-00911-1
Tokura M, Nakayama J, Prieto-Vila M, Shiino S, Yoshida M, Yamamoto T, Watanabe N, Takayama S, Suzuki Y, Okamoto K, Ochiya T, Kohno T, Yatabe Y, Suto A, Yamamoto Y. Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ. Cancer Res. 2022 Sep 16;82(18):3236-3248. https://doi.org/10.1158/0008-5472.CAN-22-0090
Stanton SE, Castle PE, Finn OJ, Sei S, Emens LA. Advances and challenges in cancer immunoprevention and immune interception. J Immunother Cancer. 2024 Mar 21;12(3):e007815. doi: https://doi.org/10.1136/jitc-2023-007815
Carleton N, Lotze MT. Reciprocal immune–epithelial interaction during breast cancer induction. Journal for ImmunoTherapy of Cancer. 2025;13:e011453. https://doi.org/10.1136/jitc-2024-011453