Evolution of immune infiltration and immune triad formation across early melanoma progression
Abstract
Tumor-infiltrating lymphocytes (TIL) in melanoma are a clinically important prognostic marker and are routinely used to inform patient care. However, when immune recognition of transformed melanocytes begins and how it evolves during early melanoma progression is not well understood. Using spatial transcriptomics and a unique cohort of patient-matched lesions representing multiple stages of early evolution, we investigate T cells, dendritic cells (DCs) and multi-cell immune “triads” during melanoma initiation. We find that T cell and DC density, triad density, and triad proximity to melanoma cells are elevated in regions of Stage I invasive melanoma as compared to Stage 0 in situ lesions and nevi. Further, we find that triad abundance correlates with both T cell and DC density, but is not predicted by clustering patterns of these cell types over larger spatial scales. We conclude that immune recognition of melanoma and engagement with the lesion significantly increases with progression from Stage 0 to Stage I disease. Further, using nevi that are depth-matched in the dermis to Stage I invasive lesions, we demonstrate this increased immune recognition is not a consequence of dermal invasion alone. This points to a paradigm where immune engagement of invasive melanoma reflects recognition of melanoma cell-intrinsic changes that emerge in Stage I disease.
Significance: Tumor-infiltrating lymphocytes predict better melanoma patient outcomes even in early stage disease, but how and when immune recognition of melanoma is initiated remains poorly understood. Using patient-matched lesions of multiple progression stages, we find immune engagement with melanoma strongly increases between Stage 0 in situ and Stage I invasive disease.
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BibTeX
@misc{marks2026evolution,
title = {{Evolution of immune infiltration and immune triad formation across early melanoma progression}},
author = {Kayla A Marks and Abigail Florell-Orton and Min Hu and Burke Lawlor and Scott Florell and Mitchell S Stark and Kathleen J Green and Dekker C Deacon and Frederick R Adler and Robert L Judson-Torres and Melissa Q Reeves},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762853},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762853v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Evolution of immune infiltration and immune triad formation across early melanoma progression
AU - Kayla A Marks
AU - Abigail Florell-Orton
AU - Min Hu
AU - Burke Lawlor
AU - Scott Florell
AU - Mitchell S Stark
AU - Kathleen J Green
AU - Dekker C Deacon
AU - Frederick R Adler
AU - Robert L Judson-Torres
AU - Melissa Q Reeves
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762853
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762853v1
AB - Tumor-infiltrating lymphocytes (TIL) in melanoma are a clinically important prognostic marker and are routinely used to inform patient care. However, when immune recognition of transformed melanocytes begins and how it evolves during early melanoma progression is not well understood. Using spatial transcriptomics and a unique cohort of patient-matched lesions representing multiple stages of early evolution, we investigate T cells, dendritic cells (DCs) and multi-cell immune “triads” during melanoma initiation. We find that T cell and DC density, triad density, and triad proximity to melanoma cells are elevated in regions of Stage I invasive melanoma as compared to Stage 0 in situ lesions and nevi. Further, we find that triad abundance correlates with both T cell and DC density, but is not predicted by clustering patterns of these cell types over larger spatial scales. We conclude that immune recognition of melanoma and engagement with the lesion significantly increases with progression from Stage 0 to Stage I disease. Further, using nevi that are depth-matched in the dermis to Stage I invasive lesions, we demonstrate this increased immune recognition is not a consequence of dermal invasion alone. This points to a paradigm where immune engagement of invasive melanoma reflects recognition of melanoma cell-intrinsic changes that emerge in Stage I disease. Significance: Tumor-infiltrating lymphocytes predict better melanoma patient outcomes even in early stage disease, but how and when immune recognition of melanoma is initiated remains poorly understood. Using patient-matched lesions of multiple progression stages, we find immune engagement with melanoma strongly increases between Stage 0 in situ and Stage I invasive disease.
SN - 2692-8205
ER -