Transcriptional profiling of macrophages in situ in metastatic melanoma reveals localization-dependent phenotypes and function.

Abstract

Modulation of immune function at the tumor site could improve patient outcomes. Here, we analyze patient samples of metastatic melanoma, a tumor responsive to T cell-based therapies, and find that tumor-infiltrating T cells are primarily juxtaposed to CD14+ monocytes/macrophages rather than melanoma cells. Using immunofluorescence-guided laser capture microdissection, we analyze transcriptomes of CD3+ T cells, CD14 + monocytes/macrophages, and melanoma cells in non-dissociated tissue. Stromal CD14+ cells display a specific transcriptional signature distinct from CD14+ cells within tumor nests. This signature contains LY75, a gene linked with antigen capture and regulation of tolerance and immunity in dendritic cells (DCs). When applied to TCGA cohorts, this gene set can distinguish patients with significantly prolonged survival in metastatic cutaneous melanoma and other cancers. Thus, the stromal CD14+ cell signature represents a candidate biomarker and suggests that reprogramming of stromal macrophages to acquire DC function may offer a therapeutic opportunity for metastatic cancers.

• Authors: Jan Martinek, Jianan Lin, Kyung In Kim, Victor G Wang, Te-Chia Wu, Michael Chiorazzi, Hannah Boruchov, Ananya Gulati, Shamreethaa Seeniraj, Lili Sun, Florentina Marches, Paul Robson, Anthony Rongvaux, Richard A Flavell, Joshy George, Jeffrey H Chuang, Jacques Banchereau, Karolina Palucka
• Journal: Cell reports. Medicine (Cell Rep Med) Vol. 3 Issue 5 Pg. 100621 (05 17 2022) ISSN: 2666-3791 [Electronic] United States
• PMID: 35584631 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Topics

• Humans
• Macrophages
• Melanoma (genetics)
• Neoplasms, Second Primary
• Phenotype
• Skin Neoplasms (genetics)
• T-Lymphocytes