Year: 2022
Type: article
Abstract: Chronic T-cell receptor (TCR) signaling in the tumor microenvironment is known to promote T-cell dysfunction. However, we reasoned that poorly immunogenic tumors may also compromise T cells by impairing their metabolism. To address this, we assessed temporal changes in T-cell metabolism, fate, and function in models of B-cell lymphoma driven by Myc, a promoter of energetics and repressor of immunogenicity. Increases in lymphoma burden most significantly impaired CD4+ T-cell function and promoted regulatory T cell (Treg) and Th1-cell differentiation. Metabolomic analyses revealed early reprogramming of CD4+ T-cell metabolism, reduced glucose uptake, and impaired mitochondrial function, which preceded changes in T-cell fate. In contrast, B-cell lymphoma metabolism remained robust during tumor progression. Finally, mitochondrial functions were impaired in CD4+ and CD8+ T cells in lymphoma-transplanted OT-II and OT-I transgenic mice, respectively. These findings support a model, whereby early, TCR-independent, metabolic interactions with developing lymphomas limits T cell-mediated immune surveillance.
Source: Cancer Immunology Research
Institutions: Moffitt Cancer Center, University of South Florida
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Awards: New Therapeutic Vulnerabilities for Aggressive B-Cell Lymphoma, G2594662357, G362094, Integrated Program in Cancer and Data Science, G4150541436, G4500671257, G4551976579, G8135003176, G8238896285, Moffitt Cancer Center Support Grant, Developing chemical probes for oncogenic signaling pathways
OpenAlex ID: W4291582763