Mast Cell Infiltration and Subtype Promote Malignant Transformation of Oral Precancer and Progression of Oral Cancer

Author:

Cai Xin-Jia12ORCID,Peng Chao-Ran324ORCID,Zhang Jian-Yun324ORCID,Li Xue-Fen12ORCID,Wang Xu52ORCID,Han Ying52ORCID,Zhang He-Yu12ORCID,Peng Xin62ORCID,Li Tie-Jun324ORCID

Affiliation:

1. Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China. 1

2. National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China. 5

3. Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China. 2

4. Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, China. 6

5. Department of Oral Medicine, Peking University School and Hospital of Stomatology, Beijing, China. 3

6. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China. 4

Abstract

Abstract The role of mast cell (MC), a common myeloid-derived immune cell, in the development of oral squamous cell carcinoma (OSCC) is unclear. The aim of this study was to investigate MC infiltration in oral precancer and oral cancer. The evaluation of immune cell infiltration and its association with prognosis in OSCC used RNA sequencing and multiple public datasets. Multiplex immunofluorescence was used to explore the infiltration of MC in the microenvironment of OSCC and oral precancer and the interaction with CD8+ cells. The role of MC in OSCC progression was verified by in vivo experiments. The resting MC infiltration was mainly present in oral precancer, whereas activated MC infiltration was significantly higher in OSCC. Activated MC was associated with malignant transformation of oral precancer and poor prognosis of OSCC. In vivo studies showed that MC promoted the growth of OSCC. The infiltration of activated MC was negatively correlated with the infiltration of CD8+ T cells. The subtype of MC containing tryptase without chymase (MCT) was significantly higher in OSCC compared with oral precancer and was associated with poor survival. Furthermore, spatial distance analysis revealed a greater distance between MCT and CD8+ cells, which was also linked to poor prognosis in OSCC. Cox regression analysis showed that MCT could be a potential diagnostic and prognostic biomarker. This study provides new insights into the role of MC in the immune microenvironment of OSCC. It might enhance the immunotherapeutic efficacy of OSCC by developing targeted therapies against MC. Significance: In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs.

Publisher

American Association for Cancer Research (AACR)

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