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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
Science immunology, 04/2022, Letnik: 7, Številka: 70Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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