The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution
Cancer Discovery. 2022;12(6):1518-1541. DOI 10.1158/2159-8290.CD-21-1357. PMID 35404441. PMCID PMC9167783.
How to cite
AMA
Nirmal AJ, Maliga Z, Vallius T, Quattrochi B, Chen AA, Jacobson CA, et al. The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution. Cancer Discov. 2022;12(6):1518-1541. doi:10.1158/2159-8290.CD-21-1357APA
Nirmal, A. J., Maliga, Z., Vallius, T., Quattrochi, B., Chen, A. A., Jacobson, C. A., et al. (2022). The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution. Cancer Discovery, 12(6), 1518-1541. https://doi.org/10.1158/2159-8290.CD-21-1357BibTeX
@article{nirmal2022spatial,
title = {The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution},
author = {Nirmal, Ajit J. and Maliga, Zoltan and Vallius, Tuulia and Quattrochi, Brian and Chen, Alyce A. and Jacobson, Connor A. and others},
journal = {Cancer Discovery},
volume = {12},
number = {6},
pages = {1518--1541},
year = {2022},
doi = {10.1158/2159-8290.CD-21-1357},
pmid = {35404441}
}Primary melanoma is usually caught early and removed, but some tumors progress from a thin, curable lesion to an invasive, dangerous one. Pathologists grade these stages by eye on stained tissue, yet what actually changes in the tumor and its surrounding immune cells as melanoma advances has been hard to see cell by cell.
The authors built a spatial, single-cell map of 13 primary melanomas that each contained several progression stages in one specimen. Using high-plex whole-slide imaging, they tracked how tumor cells and immune cells rearrange from precursor lesions through invasive disease, and found layered immune-suppressive barriers concentrated at the tumor's invasive front.
Key findings
- Thirteen primary melanomas, each spanning several progression stages, were mapped at single-cell resolution. Serial FFPE sections were imaged by whole-slide 20- to 30-plex cyclic immunofluorescence (CyCIF), with 70 annotated regions of interest analyzed across the cohort.
- Roughly 70% of cytotoxic T cells expressed the activation marker PD1, but very few tumor cells expressed PDL1. The authors concluded that myeloid cells, not tumor cells, are the predominant source of PDL1 engaging PD1-positive T cells at the invasive front.
- The invasive front carried at least six overlapping immune-suppressive mechanisms operating within a few millimeters of one another. These ranged from PD1–PDL1 cell contacts to tumor-intrinsic MHC-II and IDO1 expression, with active immunoediting found within millimeters of near-complete immune exclusion.
CyteFinder in the methods
“Images were acquired using a CyteFinder slide scanning fluorescence microscope (RareCyte Inc.) with a 20×/0.75 NA objective.”
— Nirmal et al., Cancer Discovery (2022), Methods, “Imaging (H&E and Tissue-Based CyCIF)”
Disclosure: RareCyte is named in the competing-interests statement of the publication cited above.
Why it matters for CyteFinder users
If you are considering the CyteFinder for a tissue-imaging program, this melanoma atlas shows what it carries at scale. The study's argument is spatial: to see how melanoma progresses, the authors imaged whole slides rather than small cores, because the features that matter — where cytotoxic T cells engage tumor cells, how immune suppression concentrates at the invasive front — only resolve across an entire section. They ran 20- to 30-plex cyclic immunofluorescence on thirteen primary melanomas, acquiring every staining cycle on the CyteFinder and stitching the cycles into whole-slide, single-cell images that span multiple progression stages in one specimen. The same instrument then did double duty: its integrated CytePicker module physically retrieved 40-micron tissue microregions for downstream transcriptomics, so imaging and molecular sampling came from the same annotated tissue. For your own work the point is direct: when the biology lives across a whole specimen, the CyteFinder is the instrument that both images it and picks from it.
