Single‐cell RNA sequencing reveals distinct immune cell subsets in phalangeal and soft‐tissue recurrence of giant cell tumor of bone

Author:

Yang Meiling12,Wang Fen3,Liang Huishan3,Ji Genxin4,Lian Yating3,Zou Changye5,Zhao Wei126ORCID

Affiliation:

1. Guangdong Cardiovascular Institute Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences Guangzhou China

2. Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou China

3. Department of Pathology The First Affiliated Hospital of Sun Yat‐Sen University Guangzhou China

4. The Second School of Clinical Medicine Southern Medical University Guangzhou China

5. Musculoskeletal Oncology Department The First Affiliated Hospital of Sun Yat‐Sen University Guangzhou China

6. Key Laboratory of Stem Cells and Tissue Engineering Ministry of Education Sun Yat‐Sen University Guangzhou China

Abstract

AbstractBackgroundGiant cell tumor of the bone (GCTB), an intermediate locally aggressive neoplasm that frequently involves the epiphyseal region of the long bones. GCTB of the distal phalanx and soft‐tissue recurrences are extremely rare. Little is known about the cellular and molecular differences between GCTB of the long bones and rare sites.MethodsWe employed single‐cell RNA sequencing to elucidate the transcriptional profiles of 28,992 cells originating from patients afflicted with GCTB in the femur, distal phalanx, and soft‐tissue relapse. To confirm the critical findings, we subjected the paraffin sections of GCTB to immunohistochemical staining.ResultsOur study revealed that GCTBs in rare sites display distinct immune subtypes and antigen presentation gene signatures. We observed minimal lymphocyte infiltration in GCTBs of the phalanx. Further analyses demonstrated that the transforming growth factor‐β pathway and profibrotic proteins were significantly upregulated in phalanx lesions. In contrast, GCTB cells from soft‐tissue recurrence exhibited discernible chondrocyte characteristics but presented lower antigen‐presenting ability compared to those from femur lesions. Notably, we identified an immunosuppressive subset of mast cells in the soft‐tissue recurrence. The secretion of proangiogenic and immunosuppressive factors from these mast cells suggests their potential role in the formation of vascular‐rich and immunosuppressive niches in recurrent lesions.ConclusionsCollectively, this study broadens our comprehension of the gene expression patterns observed in infrequent location GCTBs and furnishes a repository of information for illuminating promising therapeutic targets for rare GCTBs.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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