| Autor: |
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. |
| Předmět: |
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| Zdroj: |
Science Immunology; 2022, Vol. 7 Issue 70, p1-15, 15p |
| 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. Spacing of immune cells matters: A better understanding of the tumor immune microenvironment can determine biomarkers of immunotherapy effectiveness. Moldoveanu et al. used cytometry time-of-flight (CyTOF) imaging mass cytometry (IMC) to characterize the immune microenvironment of melanoma patient samples. CyTOF IMC identified the spatial arrangement and proximity of immune cells to each other. The researchers observed that a closer proximity of antigen-experienced cytotoxic T cells to melanoma cells intratumorally correlated to a patient's responsiveness to immune checkpoint blockade. Thus, spatial characterization of the tumor immune microenvironment using CyTOF IMC allows for the identification of prognostic biomarkers for immunotherapy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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