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| Content Provider | frontiers |
|---|---|
| Author | Yang, Meiling Wang, Fen Lu, Guohao Cheng, Mingzhe Zhao, Wei Zou, Changye |
| Abstract | Denosumab (DMAB), a human monoclonal antibody against the receptor activator of the nuclear factor-kappa B ligand, is used for the treatment for unresectable giant cell tumor of bone (GCTB). However, little is known about the molecular and functional characteristics of GCTB-infiltrating lymphocytes after DMAB treatment. Here, we performed single-cell RNA sequencing and immunostaining assays to delineate the immune landscape of GCTB in the presence and absence of DMAB. We found that exhausted CD8+ T cells were preferentially enriched in DMAB-treated GCTB. A distinct M2-skewed type of tumor-associated macrophages (TAMs) comprises the majority of GCTB TAMs. We identified cytokines, including interleukin-10, and inhibitory receptors of M2 TAMs as important mediators of CD8+ T cell exhaustion. We further revealed that DMAB treatment notably increased the expression levels of periostin (POSTN) in GCTB cells. Furthermore, POSTN expression was transcriptionally regulated by c-FOS signaling and correlated with GCTB recurrence in patients after DMAB treatment. Collectively, our findings reveal that CD8+ T-cells undergo unappreciated exhaustion during DMAB therapy and that GCTB cell-derived POSTN educates TAMs and establishes a microenvironmental niche that facilitates GCTB recurrence. |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2022.934078 |
| Volume Number | 13 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2022-09-12 |
| Access Restriction | Open |
| Subject Keyword | Periostin Denosumab Single-cell RNA-seq RANKL Giant Cell Tumor of Bone T-cell exhaustion |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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