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RNA sequencing of sorted immune cells from WT and CD4Cre-Yapfloxed mice from tumors and tumor-draining lymph nodes

ABSTRACT: We report the effect of T cell lineage-specific Yap deletion on tumor immunity in the B16F10 melanoma mouse model.

ORGANISM(S): Mus musculus

PROVIDER: GSE139883 | GEO | 2019/12/11

REPOSITORIES: GEO

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Single-Cell Gene Expression Profiling of CD45+ Cells from Tumors and Draining Lymph Nodes in Trp1 CD4+ T Cell-Treated B16F10 Melanoma-Bearing Mice

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Chemotherapy but Not the Tumor Draining Lymph Nodes Determine the Immunotherapy Response in Secondary Tumors.

Project description:Immunotherapies are used as adjuvant therapies for cancers. However, knowledge of how traditional cancer treatments affect immunotherapies is limited. Using mouse models, we demonstrate that tumor-draining lymph nodes (TdLNs) are critical for tumor antigen-specific T cell response. However, removing TdLNs concurrently with established primary tumors did not affect the immune checkpoint blockade (ICB) response on localized secondary tumor due to immunotolerance in TdLNs and distribution of antigen-specific T cells in peripheral lymphatic organs. Notably, treatment response improved with sequential administration of 5-fluorouracil (5-FU) and ICB compared with concurrent administration of ICB with 5-FU. Immune profiling revealed that using 5-FU as induction treatment increased tumor visibility to immune cells, decreased immunosuppressive cells in the tumor microenvironment, and limited chemotherapy-induced T cell depletion. We show that the effect of traditional cytotoxic treatment, not TdLNs, influences immunotherapy response in localized secondary tumors. We postulate essential considerations for successful immunotherapy strategies in clinical conditions.

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RNA sequencing of sorted immune cells from WT and CD4Cre-Yapfloxed mice from tumors and tumor-draining lymph nodes

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Transcriptional remodeling of lymphatic endothelial cells from tumor-draining lymph nodes in melanoma

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