The following is a summary of “Ewing Sarcoma and Osteosarcoma Have Distinct Immune Signatures and Intercellular Communication Networks” published in the November 2022 issue of Clinical Cancer by Cillo et al.

Adolescents are disproportionately affected by the principal bone sarcomas, Ewing sarcoma, and osteosarcoma. The prognosis is very poor for those with metastatic or recurrent illnesses. Current immunotherapeutic techniques for the treatment of bone sarcomas have needed to be more effective, needing a deeper understanding of bone sarcoma immunobiology, notwithstanding their success in treating some soft tissue sarcomas. Immune infiltration in primary and recurrent illness was compared using multiplex immunofluorescence analysis. Single-cell RNA sequencing (scRNAseq) of immune populations from paired blood and bone sarcoma tumor samples was undertaken to better understand immunological states and drivers of immune infiltration, particularly during disease progression.

Based on our multiplex immunofluorescence investigation results, we found that relapsed Ewing sarcoma and recurrent osteosarcoma exhibit higher immune infiltration than the initial disease. scRNAseq studies uncovered an effector T-cell subset in Ewing sarcoma and co-inhibitory receptor-expressing CD8+T cells at the end of their lives in osteosarcoma. The Ewing sarcoma and osteosarcoma tumor microenvironments also contained unique populations of CD14+CD16+ macrophages. 

Following intercellular communication analyses, we identified common methods of immune infiltration driven by CD14+CD16+ macrophages and distinct pathways of immune infiltration driven by CXCL10 and CXCL12 in osteosarcoma, revealing the molecular processes underlying tumor immune infiltration.their research is a valuable repository of immunologic data from bone sarcomas and provides the preclinical rationale for future evaluation of specific immunotherapeutic targets upon relapse.

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