Ubiquitin‐Conjugating Enzyme Ubc13 in Macrophages Suppresses Lung Tumor Progression Through Inhibiting PD‐L1 Expression
Year: 2024
Type: article
Abstract: ABSTRACT Tumor cell‐intrinsic ubiquitin‐conjugating enzyme Ubc13 promotes tumorigenesis, yet how Ubc13 in immune cell compartments regulates tumor progression remains elusive. Here, we show that myeloid‐specific deletion of Ubc13 ( Ubc13 fl/fl Lyz2 Cre ) leads to accelerated transplanted lung tumor growth in mice. Compared with their littermate controls, tumor‐bearing Ubc13 fl/fl Lyz2 Cre mice had lower proliferation and effector function of CD8 + T lymphocytes, accompanied by increased infiltration of myeloid‐derived suppressor cells within the tumor microenvironment. Mechanistically, Ubc13 deficiency leads to upregulation of Arg1 and PD‐L1, the latter is modulated by reduced Ubc13‐mediated K63‐linked polyubiquitination and increasing activation of Akt, thereby inducing skewness to protumoral polarization and immunosuppressive manifestation. Taken together, we reveal that macrophage‐intrinsic Ubc13 restrains lung tumor progression, indicating that activating Ubc13 in macrophages could be an effective immunotherapeutic regimen for lung cancer.
Source: European Journal of Immunology
Authors: Siying Sun, Jun Ni, Jiamin Liu, Juofang Tan, Runsen Jin, Hecheng Li, Xuefeng Wu
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: Shanghai Municipal Health Commission, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Shanghai Jiao Tong University, Peking University, University of Texas MD Anderson Cancer Center, National Key Research and Development Program of China, Program of Shanghai Academic Research Leader, Science and Technology Innovation Plan Of Shanghai Science and Technology Commission
OpenAlex ID: W4405727415