Document Type

Article

Publication Date

5-17-2022

Publication Title

Cell Rep Med

Keywords

JGM, Humans, Macrophages, Melanoma, Neoplasms, Second Primary, Phenotype, Skin Neoplasms, T-Lymphocytes

JAX Source

Cell Rep Med 2022 May 17; 3(5):100621

Volume

3

Issue

5

First Page

100621

Last Page

100621

ISSN

2666-3791

PMID

35584631

DOI

https://doi.org/10.1016/j.xcrm.2022.100621

Grant

CA034196, CA195712, CA204115, CA230031

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.

Comments

We thank The Microscopy, Single Cell Biology, Genome Technology, and CTRS Scientific Services of JAX.

This is an open access article under the CC BY-NC-ND license

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