NGF-NGFR communication inefficiency induces T Cell exhaustion impairing PD-1 immunotherapy in hepatocellular carcinoma DOI Creative Commons

Tongwang Yang,

Qingguo Xu,

Chuanshen Xu

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 5, 2023

Abstract The number of T cells that infiltrate tumor tissues in hepatocellular carcinoma (HCC) is significantly low. molecular mechanism underlying cell proliferation poorly understood. present study revealed during the process infiltration from adjacent to tissues, NGF-NGFR communication inefficiency occurred HCC patients. Importantly, cell-secreted NGF interacted with NGFR on membranes infiltrated cells, which promoted these through mitotic spindle signal activation. Mechanistically, activation was mediated by HDAC1 unclear trans-localization-inhibited PREX1 expression. Further, PD-1 mAb acted synergistically suppress progression both mouse model and In addition, NGF–NGFR positively correlated PD-1/PDL-1 However, expressions were low responsible for incursive clinicopathological features disappointing prognosis Collectively, results suggested impaired immunotherapy could, therefore, be utilized as a novel therapeutic target treatment patients clinical practice.

Language: Английский

NGF-NGFR communication inefficiency induces T Cell exhaustion impairing PD-1 immunotherapy in hepatocellular carcinoma DOI Creative Commons

Tongwang Yang,

Qingguo Xu,

Chuanshen Xu

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 5, 2023

Abstract The number of T cells that infiltrate tumor tissues in hepatocellular carcinoma (HCC) is significantly low. molecular mechanism underlying cell proliferation poorly understood. present study revealed during the process infiltration from adjacent to tissues, NGF-NGFR communication inefficiency occurred HCC patients. Importantly, cell-secreted NGF interacted with NGFR on membranes infiltrated cells, which promoted these through mitotic spindle signal activation. Mechanistically, activation was mediated by HDAC1 unclear trans-localization-inhibited PREX1 expression. Further, PD-1 mAb acted synergistically suppress progression both mouse model and In addition, NGF–NGFR positively correlated PD-1/PDL-1 However, expressions were low responsible for incursive clinicopathological features disappointing prognosis Collectively, results suggested impaired immunotherapy could, therefore, be utilized as a novel therapeutic target treatment patients clinical practice.

Language: Английский

Citations

0