2026-10-14T06:48:11Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34054548 2026-10-02T05:37:09Z category_696 portal_316 item_type_3 month_year_10_2026

Data Sheet 1_Chronic XBP1s-mediated activation of the unfolded protein response impairs CD8+ T cell anti-tumor immunity.pdf Keith Alan Nair (25162620) Jessica Lee (733479) Olivia Zaleski (25162623) Luciano Mazzoccoli (12588049) Brian Deng (25162626) Chih-Chi Andrew Hu (1320063) Stanley Ching-Cheng Huang (9211331) Andreas Wieland (543841) Hazem E. Ghoneim (17930500) Haitao Wen (206662) Xiaopei Huang (251829) Bei Liu (311802) Genetic Immunology anti-tumor immunity CD8+ T cells T cell exhaustion unfolded protein response XBP1s <p>CD8⁺ T cells play a crucial role in anti-tumor immunity; however, their functionality is compromised by exhaustion driven by chronic antigen exposure, poor tumor microenvironment, and metabolic dysfunction. Activated CD8⁺ T cells undergo extensive proteomic remodeling, which includes the induction of the IRE1-XBP1 signaling axis of the unfolded protein response. However, the functional consequences of sustained IRE1-XBP1 activation in exhausted CD8⁺ T cells remain elusive. Using a model of constitutive XBP1 activation in CD8⁺ T cells, we demonstrate that sustained XBP1s signaling leads to reduced homeostatic CD8⁺ T cell populations, impaired migratory capacity, and dampened anti-tumor immunity. Notably, pharmacological inhibition of the IRE1-XBP1 axis significantly reduces tumor burden through a dual mechanism that targets both tumor cells and the immune compartment. Our findings reveal a previously unappreciated role for XBP1s in regulating CD8⁺ T cell biology and highlight the IRE1-XBP1 axis as a therapeutic target in solid tumors.</p> 2026-10-02T05:37:09Z Dataset Dataset 10.3389/fimmu.2026.1940201.s002 https://figshare.com/articles/dataset/Data_Sheet_1_Chronic_XBP1s-mediated_activation_of_the_unfolded_protein_response_impairs_CD8_T_cell_anti-tumor_immunity_pdf/34054548 CC BY 4.0