Biology subjects

Gray-Gaillard, S. L.

Publications and source records attributed to Gray-Gaillard, S. L..

2 recordsLinked to original sources

bioRxiv2025

Cellular interactions in the sentinel lymph node predict melanoma recurrence

Melanoma outcomes have dramatically improved over the past decade, but some patients still experience disease recurrence, particularly those who present at later stage of disease. Prior studies identified an altered immune microenvironment in the sentinel lymph node (SLN) including the presence of dysfunctional CD8 T cells and CD4 T regulatory cells (Tregs), but the spatial organization of the SLN and the interactions of individual cell types have not been extensively studied. To understand how spatial organization of immune cells in the SLN is related to outcomes, we performed spatial proteomic profiling of Stage I and II melanoma SLN to generate an atlas of cell types. Following multiplexed immunofluorescence imaging, deep learning-based segmentation and clustering, we identified 33 subsets of T cells, B cells and Tumor cells. Lymphoid region analyses established a foundational spatial map of the melanoma SLN, revealing higher regional frequencies of activated and memory CD4 T cells in Stage I SLN and consistent positioning of T cells at functional spatial locations. To better understand cellular interactions, we evaluated the immediate neighbors around each index cell using Effect Size Interaction mapping (ESI-map), a novel computational toolkit for understanding spatial interactions. Nearest-neighbor analyses across biological replicates revealed rewiring in cell-cell interacting pairs across disease progression and patient outcomes, particularly with respect to exhausted TOX+ CD8 T cells. Stage II patients who experienced disease recurrence had notable enrichment of cellular interactions between Tregs and TOX+ CD8 T cells that was associated with reduced expression of granzyme B and interferon-{gamma} that was most pronounced in exhausted CD8 T cells. Together, these data demonstrate that the specific spatial interactions between Tregs and exhausted CD8 T cells in the SLN provide a novel immune signature for understanding melanoma outcomes. One Line SummaryTreg-CD8 T cell interactions in the sentinel lymph node predict recurrence outcomes in Stage II SLN+ melanoma patients.

immunology↗

bioRxiv2022

Molecularly distinct memory CD4+ T cells are induced by SARS-CoV-2 infection and mRNA vaccination

Adaptive immune responses are induced by vaccination and infection, yet little is known about how CD4+ T cell memory differs when primed in these two contexts. Notably, viral infection is generally associated with higher levels of systemic inflammation than is vaccination. To assess whether the inflammatory milieu at the time of CD4+ T cell priming has long-term effects on memory, we compared Spike-specific memory CD4+ T cells in 22 individuals around the time of the participants third SARS-CoV-2 mRNA vaccination, with stratification by whether the participants first exposure to Spike was via virus or mRNA vaccine. Multimodal single-cell profiling of Spike-specific CD4+ T cells revealed 755 differentially expressed genes that distinguished infection- and vaccine-primed memory CD4+ T cells. Spike-specific CD4+ T cells from infection-primed individuals had strong enrichment for cytotoxicity and interferon signaling genes, whereas Spike-specific CD4+ T cells from vaccine-primed individuals were enriched for proliferative pathways by gene set enrichment analysis. Moreover, Spike-specific memory CD4+ T cells established by infection had distinct epigenetic landscapes driven by enrichment of IRF-family transcription factors, relative to T cells established by mRNA vaccination. This transcriptional imprint was minimally altered following subsequent mRNA vaccination or breakthrough infection, reflecting the strong bias induced by the inflammatory environment during initial memory differentiation. Together, these data suggest that the inflammatory context during CD4+ T cell priming is durably imprinted in the memory state at transcriptional and epigenetic levels, which has implications for personalization of vaccination based on prior infection history. One Sentence SummarySARS-CoV-2 infection versus SARS-CoV-2 mRNA vaccination prime durable transcriptionally and epigenetically distinct Spike-specific CD4+ T cell memory landscapes.

immunology↗