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Abstract #4528

Tumor-induced metabolic reprogramming and CD8+ T-cell exhaustion of the spleen

James D Barnett1, Marie-France Penet 1,2, Raj Kumar Sharma1, Michal Stanczak3, Saleem Yousf1, Balaji Krishnamachary1, Yelena Mironchik1, Erika L Pearce3, and Zaver M Bhujwalla1,2,4
1Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, United States, 2Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States, 3Bloomberg-Kimmel Institute of Immunotherapy, Baltimore, MD, United States, 4Department of Radiation Oncology and Molecular Radiation Sciences, Baltimore, MD, United States

Synopsis

Keywords: Probes & Targets, Tumor, Spleen

Motivation: Metastasis is the leading cause of cancer-related mortality worldwide. We must pave new avenues for cancer treatment by interrogating the pro-tumorigenic properties of the tumor macroenvironment.

Goal(s): We seek to investigate how tumorigenesis metabolically impacts the spleen microenvironment and how it contributes to immune evasion.

Approach: Proton magnetic resonance spectroscopy was used to identify aqueous spleen metabolites during tumorigenesis. Flow cytometric analyses were conducted to immunophenotype splenic CD8+ T cells and to quantify MDSC and T-cell frequencies.

Results: Tumorigenesis induced common, distinct metabolite changes in mouse spleens. Flow cytometric analyses revealed splenic CD8-T-cell exhaustion and reduced cytotoxic T-cell effector function.

Impact: Tumors drive metabolic spleen alterations that may contribute to reduced CD8+ T cells and their exhaustion even before reaching the tumor, contributing to immune suppression and poor prognosis. This may provide metabolism-targeted strategies to improve immune surveillance and immunotherapy.

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