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- W4366171488 abstract "The purpose of this study was to determine if a multiplex immunofluorescence (mIF) assay could be used to identify patients (pts) with advanced melanoma who benefit from the addition of anti-CTLA-4 therapy to their anti-PD-1 regimen. We previously developed a 6-plex mIF assay (Sox10/S100, PD-1, PD-L1, FoxP3, CD8, CD163) to predict long-term survival in pts after anti-PD-1-based therapy. Pre-treatment specimens from a discovery cohort of 53 pts with advanced melanoma who later received anti-PD-1 therapy (34 with anti-PD-1 monotherapy, 19 with anti-PD-1+CTLA-4 combinatorial therapy) were stained with the mIF assay and mapped using the AstroPath platform. The spatially-mapped specific immunomodulatory molecule expression was used to classify pts into three distinct TME profiles (‘good,’ ‘intermediate,’ & ‘poor’) that correlated with long-term survival by Kaplan-Meier analysis. Pts with ‘good’ pre-treatment TMEs, which had high CD8+FoxP3+ cell densities, did not show differences in overall survival (OS) between those receiving combinatorial vs. monotherapy. Importantly, pts with ‘intermediate’ pre-treatment TMEs, which had low-level CD8+ immune infiltrates and were not CD163+PD-L1- myeloid-rich, showed improved 3-yr. OS with combinatorial vs. monotherapy (p=0.04). Pts with ‘poor’ pre-treatment TMEs, which had high densities of tumor cells and CD163+PD-L1-myeloid cells, derived the least benefit from these standard-of-care regimens. In conclusion, pts with ‘good’ pre-treatment TMEs do not benefit from the addition of anti-CTLA-4, may be appropriately treated with monotherapy, and spared the potential side effects of combinatorial therapy. Pts with the distinct ‘intermediate’ TME benefit from and should be treated with combinatorial therapy. Pts with ‘poor’ pre-treatment TMEs may benefit from pursuing alternative therapies, including those being tested in clinical trials. These findings warrant further exploration, including validation in an independent cohort, which is currently underway." @default.
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- W4366171488 date "2023-05-01" @default.
- W4366171488 modified "2023-10-16" @default.
- W4366171488 title "589 Patients with advanced melanoma who benefit from the addition of anti-CTLA-4 to anti-PD-1 have a distinct tumor microenvironment (TME)" @default.
- W4366171488 doi "https://doi.org/10.1016/j.jid.2023.03.596" @default.
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