NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinoma

Abstract Salivary adenoid cystic carcinoma (SACC) with a unique MYB‐NFIB fusion has been considered an “immune‐cold” tumor, but the mechanisms behind this remain unclear. In this study, we analyzed the immune status of 29 SACC patients and found that most lung metastases exhibited an immunoinflammat...

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Main Authors: Ge‐xuan Feng, Meng‐jiao Zhou, Lin Cao, Ting‐yao Ma, Xue‐lian Wang, Ran Gao, Xiao‐hong Chen, Lu Kong
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:MedComm – Oncology
Subjects:
Online Access:https://doi.org/10.1002/mog2.29
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author Ge‐xuan Feng
Meng‐jiao Zhou
Lin Cao
Ting‐yao Ma
Xue‐lian Wang
Ran Gao
Xiao‐hong Chen
Lu Kong
author_facet Ge‐xuan Feng
Meng‐jiao Zhou
Lin Cao
Ting‐yao Ma
Xue‐lian Wang
Ran Gao
Xiao‐hong Chen
Lu Kong
author_sort Ge‐xuan Feng
collection DOAJ
description Abstract Salivary adenoid cystic carcinoma (SACC) with a unique MYB‐NFIB fusion has been considered an “immune‐cold” tumor, but the mechanisms behind this remain unclear. In this study, we analyzed the immune status of 29 SACC patients and found that most lung metastases exhibited an immunoinflammatory state, in contrast to the primary SACC tissues. Single‐cell sequencing data showed that anergic T‐cell types were low in primary inflammatory tissues, while inflammatory metastatic lung tissues had elevated levels of anergic CD8+ natural killer T (NKT)‐like cells and low levels of memory T cells. Primary exclusive tissues had high levels of myeloid‐derived suppressor cells (MDSCs) and low levels of activated CD8+ NKT‐like cells. These data support the fact that metastatic SACC cells might induce a stronger immune response in the lung. Additionally, an in vivo experiment showed that a minimally invasive SACC cell line with higher expression of human leukocyte antigens ‐B and ‐C induced NKT cell activation in mice and effectively attenuated the incidence of lung metastases caused by a highly invasive SACC cell line. This suggests that NKT therapy may be active in treating SACC lung metastasis. Conclusively, this study sheds light on the immune microenvironment of SACC and highlights the potential of NKT‐based therapy.
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spelling doaj.art-ff85ec4d99904305b5a25e6258bf71852023-10-09T10:56:48ZengWileyMedComm – Oncology2769-64482023-06-0122n/an/a10.1002/mog2.29NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinomaGe‐xuan Feng0Meng‐jiao Zhou1Lin Cao2Ting‐yao Ma3Xue‐lian Wang4Ran Gao5Xiao‐hong Chen6Lu Kong7Department of Biochemistry and Molecular Biology Capital Medical University Beijing ChinaDepartment of Otolaryngology‐Head and Neck Surgery, Beijing Tongren Hospital Capital Medical University Beijing ChinaDepartment of Otolaryngology‐Head and Neck Surgery, Beijing Tongren Hospital Capital Medical University Beijing ChinaDepartment of Otolaryngology‐Head and Neck Surgery, Beijing Tongren Hospital Capital Medical University Beijing ChinaDepartment of Otolaryngology‐Head and Neck Surgery, Beijing Tongren Hospital Capital Medical University Beijing ChinaChronic Disease Research Center, NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases Institute of Laboratory Animal Sciences, CAMS & PUMC Beijing ChinaDepartment of Otolaryngology‐Head and Neck Surgery, Beijing Tongren Hospital Capital Medical University Beijing ChinaDepartment of Biochemistry and Molecular Biology Capital Medical University Beijing ChinaAbstract Salivary adenoid cystic carcinoma (SACC) with a unique MYB‐NFIB fusion has been considered an “immune‐cold” tumor, but the mechanisms behind this remain unclear. In this study, we analyzed the immune status of 29 SACC patients and found that most lung metastases exhibited an immunoinflammatory state, in contrast to the primary SACC tissues. Single‐cell sequencing data showed that anergic T‐cell types were low in primary inflammatory tissues, while inflammatory metastatic lung tissues had elevated levels of anergic CD8+ natural killer T (NKT)‐like cells and low levels of memory T cells. Primary exclusive tissues had high levels of myeloid‐derived suppressor cells (MDSCs) and low levels of activated CD8+ NKT‐like cells. These data support the fact that metastatic SACC cells might induce a stronger immune response in the lung. Additionally, an in vivo experiment showed that a minimally invasive SACC cell line with higher expression of human leukocyte antigens ‐B and ‐C induced NKT cell activation in mice and effectively attenuated the incidence of lung metastases caused by a highly invasive SACC cell line. This suggests that NKT therapy may be active in treating SACC lung metastasis. Conclusively, this study sheds light on the immune microenvironment of SACC and highlights the potential of NKT‐based therapy.https://doi.org/10.1002/mog2.29immune checkpoint therapyimmune ecosystemNKT cellsalivary adenoid cystic carcinomasingle‐cell sequencing
spellingShingle Ge‐xuan Feng
Meng‐jiao Zhou
Lin Cao
Ting‐yao Ma
Xue‐lian Wang
Ran Gao
Xiao‐hong Chen
Lu Kong
NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinoma
MedComm – Oncology
immune checkpoint therapy
immune ecosystem
NKT cell
salivary adenoid cystic carcinoma
single‐cell sequencing
title NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinoma
title_full NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinoma
title_fullStr NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinoma
title_full_unstemmed NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinoma
title_short NKT cells contribute to alleviating lung metastasis in adenoid cystic carcinoma
title_sort nkt cells contribute to alleviating lung metastasis in adenoid cystic carcinoma
topic immune checkpoint therapy
immune ecosystem
NKT cell
salivary adenoid cystic carcinoma
single‐cell sequencing
url https://doi.org/10.1002/mog2.29
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