Upregulation of peripheral CD4+CXCR5+ T cells in osteosarcoma.

Immune dysregulation plays a key role in the development of osteosarcoma (OS). Peripheral blood CD4+CXCR5+ T cells can induce B-cell activation and produce various cytokines and therefore may play critical roles in tumorigenesis. The purpose of the study was to investigate changes of peripheral CD4+CXCR5+ T cells in OS. Peripheral CD4+CXCR5+ T cells and its subtypes were determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 in 38 OS patients and 42 healthy controls using flow cytometry. Data demonstrated that percentage of peripheral CD4+CXCR5+ T cells was significantly increased in OS patients (13.9 %) than in controls (8.6 %, p<0.001). Further analysis identified a profound skewing of peripheral CD4+CXCR5+ T cell subsets toward Th2 and Th17 cells in OS patients. Investigating clinical status of the patients showed that prevalence of peripheral CD4+CXCR5+ T cells was significantly elevated in cases with metastasis (17.4 %) than those without metastasis (12.7 %). Similarly, patients with high tumor grade revealed increased percentage of CD4+CXCR5+ T cells compared to those with low tumor grade (15.3 versus 11.0 %). Interestingly, the upregulation of peripheral CD4+CXCR5+ T cells in patients with metastasis or high tumor grade was contributed by Th1 and Th17 subtypes. This study suggests the involvement of peripheral CD4+CXCR5+ T cells in the pathogenesis and progression of OS and provides novel knowledge for understanding this disease.