Spatially mapping the immune landscape of melanoma using imaging mass cytometry

• Published in: Science immunology Vol. 7; no. 70; p. eabi5072
• Main Authors: Moldoveanu, Dan, Ramsay, LeeAnn, Lajoie, Mathieu, Anderson-Trocme, Luke, Lingrand, Marine, Berry, Diana, Perus, Lucas J M, Wei, Yuhong, Moraes, Cleber, Alkallas, Rached, Rajkumar, Shivshankari, Zuo, Dongmei, Dankner, Matthew, Xu, Eric Hongbo, Bertos, Nicholas R, Najafabadi, Hamed S, Gravel, Simon, Costantino, Santiago, Richer, Martin J, Lund, Amanda W, Del Rincon, Sonia V, Spatz, Alan, Miller, Jr, Wilson H, Jamal, Rahima, Lapointe, Réjean, Mes-Masson, Anne-Marie, Turcotte, Simon, Petrecca, Kevin, Dumitra, Sinziana, Meguerditchian, Ari-Nareg, Richardson, Keith, Tremblay, Francine, Wang, Beatrice, Chergui, May, Guiot, Marie-Christine, Watters, Kevin, Stagg, John, Quail, Daniela F, Mihalcioiu, Catalin, Meterissian, Sarkis, Watson, Ian R
• Format: Journal Article
• Language: English
• Published: United States 01.04.2022
• Subjects: Humans; Image Cytometry; Lymphocytes, Tumor-Infiltrating; Melanoma; T-Lymphocytes, Cytotoxic; Tumor Microenvironment
• ISSN: 2470-9468
• DOI: 10.1126/sciimmunol.abi5072

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.