2026-10-14T05:14:01Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33828724 2026-09-16T05:33:00Z category_696 portal_316 item_type_3 month_year_09_2026

Data Sheet 1_Ras protein activator-like 3 is a key Ras GTPase-activating protein that protects the survival and anti-tumor activity of CD8+ T cells.pdf Zhenzi Peng (6005783) Xinyi Zhou (3594002) Alato Okuno (3252636) Derick Okwan-Duodu (11611843) Suguru Saito (4557757) Genetic Immunology anti-tumor immunity CD8+ T cells melanoma RASAL3 RasGAP <p>Ras signaling plays an essential role in immune cell function; however, its activity must be precisely controlled to prevent excessive activation and associated cellular dysfunction. In this study, we identify the leukocyte-specific Ras GTPase-activating protein (RasGAP) RASAL3 as an important regulator of CD8⁺ T cell homeostasis and anti-tumor immunity. Following T cell receptor (TCR) stimulation, RASAL3-deficient CD8⁺ T cells display sustained Ras activation, resulting in increased activation-induced cell death (AICD). The surviving RASAL3-deficient CD8⁺ T cells exhibit impaired effector functions, including reduced cytokine production and decreased tumor-killing activity. Using an in vivo B16-F10 melanoma model, we found that CD8⁺ T cell-specific RASAL3-deficient mice (R3^fl/flCd8-Cre) develop significantly faster tumor growth compared with control mice. Although Programmed death protein 1 (PD-1) blockade partially restores anti-tumor responses in these mice, the therapeutic effect remains markedly weaker than that observed in control animals. In human melanoma samples, RASAL3 expression is reduced in tumor-infiltrating CD8⁺ T cells. Furthermore, patients with metastatic melanoma show lower RASAL3 expression in primary tumors compared with patients without metastasis, and higher RASAL3 expression in CD8⁺ T cells within primary lesions is associated with improved overall survival. Together, these findings reveal that RASAL3 is required for the maintenance of CD8⁺ T cell survival and effector activity. Reduced RASAL3 expression may represent a mechanism by which tumors evade immune surveillance, and RASAL3 expression in CD8⁺ T cells may serve as a potential biomarker for predicting clinical outcomes in melanoma.</p> 2026-09-16T05:33:00Z Dataset Dataset 10.3389/fimmu.2026.1893111 https://figshare.com/articles/dataset/Data_Sheet_1_Ras_protein_activator-like_3_is_a_key_Ras_GTPase-activating_protein_that_protects_the_survival_and_anti-tumor_activity_of_CD8_T_cells_pdf/33828724 CC BY 4.0