期刊
CLINICAL AND TRANSLATIONAL MEDICINE
卷 12, 期 4, 页码 -出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/ctm2.800
关键词
dysfunctional fingerprint; HCC; tumour Immunity; gamma delta T cell
资金
- Key Program of the National Natural Science Foundation of China [32030036, 31830021]
- Startup Foundation of the Zhuhai People's Hospital [YNXM20210305]
- Natural Science Foundation of Guangdong Province [2020A1515010132]
- National Natural Science Foundation of China [31800758, 32070882, 82002787]
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [2013A061401007, 2017B030314018]
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yatsen University, Guangzhou, China [2015B050501002]
- '111 project' of China [B16021]
This study reported the dysfunctional features of γδ T cells in hepatocellular carcinoma (HCC) within the tumor microenvironment, providing scientific support for the use of allogeneic V delta 2(+) γδ T cells in HCC immunotherapy.
In herd tocellular carcinoma (HCC), gamma delta T cells participate in mediating the antitumour response and are linked with a positive prognosis. However, these cells can become pro-tumoural in the tumour microenvironment (TME). We aimed to decipher the immune landscape and functional states of HCC-infiltrating gamma delta T cells to provide fundamental evidence for the adoptive transfer of allogeneic V delta 2(+) gamma delta T cells in HCC immunotherapy. We performed single-cell RNA sequencing (scRNA-seq) on gamma delta T cells derived from HCC tumours and healthy donor livers. Confocal microscopy, flow cytometry and a Luminex assay were applied to validate the scRNA-seq findings. The gamma delta T cells in the HCC TME entered G2/M cell cycle arrest, and expressed cytotoxic molecules such as interferon-gamma and granzyme B, but were functionally exhausted as indicated by upregulated gene and protein LAG3 expression. The gamma delta T cells in the HCC TME were dominated by the LAG3(+)V delta 1(+) population, whereas the V delta 2(+) gamma delta T population was greatly depleted. Moreover, glutamine metabolism of gamma delta T cells was markedly upregulated in the glutamine-deficient TME. Both in vitro and in vivo experiments showed that glutamine deficiency upregulated LAG3 expression. Finally, our results indicated that ex vivo-expanded V gamma delta 2(+) gamma delta T cells from healthy donor could complement the loss of T cell receptor clonality and effector functions of HCC-derived gamma delta T cells. This work deciphered the dysfunctional signatures of HCC-infiltrating gamma delta T cells in the HCC TME, providing scientific support for the use of allogeneic V delta 2(+) gamma delta T cells in HCC cellular therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据