Spatially mapping the immune landscape of melanoma using imaging mass cytometry.

Autor: Moldoveanu D; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.; McGill University Health Centre, Montréal, QC, Canada.; Department of Surgery, Division of General Surgery, McGill University, Montréal, QC, Canada., Ramsay L; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada., Lajoie M; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada., Anderson-Trocme L; McGill University Genome Centre, Montréal, QC, Canada.; Department of Human Genetics, McGill University, Montréal, QC, Canada., Lingrand M; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.; Department of Biochemistry, McGill University, Montréal, QC, Canada., Berry D; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.; Department of Biochemistry, McGill University, Montréal, QC, Canada., Perus LJM; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada., Wei Y; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada., Moraes C; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada., Alkallas R; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.; McGill University Genome Centre, Montréal, QC, Canada.; Department of Human Genetics, McGill University, Montréal, QC, Canada., Rajkumar S; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.; Department of Biochemistry, McGill University, Montréal, QC, Canada., Zuo D; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada., Dankner M; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada., Xu EH; Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Bertos NR; Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Najafabadi HS; McGill University Genome Centre, Montréal, QC, Canada.; Department of Human Genetics, McGill University, Montréal, QC, Canada., Gravel S; McGill University Genome Centre, Montréal, QC, Canada.; Department of Human Genetics, McGill University, Montréal, QC, Canada., Costantino S; Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada., Richer MJ; Indiana University School of Medicine, Indianapolis, IN, USA., Lund AW; Ronald O. Perelman Department of Dermatology and Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA., Del Rincon SV; Jewish General Hospital, McGill University, Montréal, QC, Canada.; Lady Davis Institute for Medical Research, Montréal, QC, Canada., Spatz A; McGill University Health Centre, Montréal, QC, Canada.; Lady Davis Institute for Medical Research, Montréal, QC, Canada.; McGill University, Montréal, QC, Canada., Miller WH Jr; Jewish General Hospital, McGill University, Montréal, QC, Canada.; Lady Davis Institute for Medical Research, Montréal, QC, Canada., Jamal R; Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montréal, QC, Canada., Lapointe R; Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montréal, QC, Canada.; Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada., Mes-Masson AM; Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montréal, QC, Canada.; Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada., Turcotte S; Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montréal, QC, Canada., Petrecca K; Montreal Neurological Institute and Hospital, Montréal, QC, Canada., Dumitra S; McGill University Health Centre, Montréal, QC, Canada.; Department of Surgery, Division of General Surgery, McGill University, Montréal, QC, Canada.; Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Meguerditchian AN; McGill University Health Centre, Montréal, QC, Canada.; Department of Surgery, Division of General Surgery, McGill University, Montréal, QC, Canada.; Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Richardson K; McGill University Health Centre, Montréal, QC, Canada., Tremblay F; McGill University Health Centre, Montréal, QC, Canada.; Department of Surgery, Division of General Surgery, McGill University, Montréal, QC, Canada., Wang B; McGill University Health Centre, Montréal, QC, Canada.; Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Chergui M; McGill University Health Centre, Montréal, QC, Canada., Guiot MC; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.; McGill University Health Centre, Montréal, QC, Canada.; Montreal Neurological Institute and Hospital, Montréal, QC, Canada., Watters K; McGill University Health Centre, Montréal, QC, Canada., Stagg J; Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montréal, QC, Canada., Quail DF; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.; Department of Physiology, McGill University, Montréal, QC, Canada., Mihalcioiu C; McGill University Health Centre, Montréal, QC, Canada.; Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Meterissian S; McGill University Health Centre, Montréal, QC, Canada.; Department of Surgery, Division of General Surgery, McGill University, Montréal, QC, Canada.; Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Watson IR; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada.; Department of Biochemistry, McGill University, Montréal, QC, Canada.; Research Institute of the McGill University Health Centre, Montréal, QC, Canada.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2022 Apr; Vol. 7 (70), pp. eabi5072. Date of Electronic Publication: 2022 Apr 01.
DOI: 10.1126/sciimmunol.abi5072
Abstrakt: Melanoma is an immunogenic cancer with a high response rate to immune checkpoint inhibitors (ICIs). It harbors a high mutation burden compared with other cancers and, as a result, has abundant tumor-infiltrating lymphocytes (TILs) within its microenvironment. However, understanding the complex interplay between the stroma, tumor cells, and distinct TIL subsets remains a substantial challenge in immune oncology. To properly study this interplay, quantifying spatial relationships of multiple cell types within the tumor microenvironment is crucial. To address this, we used cytometry time-of-flight (CyTOF) imaging mass cytometry (IMC) to simultaneously quantify the expression of 35 protein markers, characterizing the microenvironment of 5 benign nevi and 67 melanomas. We profiled more than 220,000 individual cells to identify melanoma, lymphocyte subsets, macrophage/monocyte, and stromal cell populations, allowing for in-depth spatial quantification of the melanoma microenvironment. We found that within pretreatment melanomas, the abundance of proliferating antigen-experienced cytotoxic T cells (CD8 + CD45RO + Ki67 + ) and the proximity of antigen-experienced cytotoxic T cells to melanoma cells were associated with positive response to ICIs. Our study highlights the potential of multiplexed single-cell technology to quantify spatial cell-cell interactions within the tumor microenvironment to understand immune therapy responses.
Databáze: MEDLINE