Expression of CCL21 in Ewing sarcoma shows an inverse correlation with metastases and is a candidate target for immunotherapy.

Abstract

Ewing sarcoma is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. For patients with metastatic disease in particular, immunotherapy has been proposed as possible beneficial additive therapy. CCL21 activation-based immunotherapy was successful in preclinical studies in other tumor types; therefore, we investigated CCL21 expression in Ewing sarcoma as potential target for immunotherapy. The CCL21 RNA expression was determined in 21 Ewing sarcoma cell lines and 18 primary therapy-naive Ewing sarcoma samples. In the tumor samples, this was correlated with the number and CD4(+)/CD8(+) ratio of infiltrating T cells and clinical parameters. Higher RNA expression levels of CCL21 significantly correlated with a lower CD4(+)/CD8(+) T cell ratio (P = 0.009), good chemotherapeutic response (P = 0.01) and improved outcome (P < 0.001). In patients with metastases, CCL21 expression was significantly lower than in patients without (P < 0.0005). CCL21 expression was significantly higher in Ewing sarcoma tissue samples compared to cell lines (P < 0.01), implying the involvement of a stromal factor. Protein expression analysis of CCL21 and its receptor CCR7 in 24 therapy-naïve tumors showed that there was no expression in all bar one Ewing sarcoma cells. In conclusion, CCL21 is expressed in clinical Ewing sarcoma samples by nontumor-infiltrating immune cells. The observed positive correlation with survival implies that CCL21 might be a potential prognostic marker for Ewing sarcoma and marks the potential of CCL21 immunotherapy for use in Ewing sarcoma.

• Authors: Laurens G L Sand, Dagmar Berghuis, Karoly Szuhai, Pancras C W Hogendoorn
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 65 Issue 8 Pg. 995-1002 (08 2016) ISSN: 1432-0851 [Electronic] Germany
• PMID: 27369431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL21 protein, human
• Chemokine CCL21

Topics

• Bone Neoplasms (genetics, pathology)
• Chemokine CCL21 (metabolism)
• Female
• Humans
• Immunotherapy
• Male
• Sarcoma, Ewing (genetics, pathology)
• Tumor Microenvironment