Dynamic changes in peripheral blood lymphocyte subsets predict the efficacy and prognosis of immune checkpoint inhibitors in metastatic osteosarcoma

BackgroundOsteosarcoma (OSA) remains the most common primary malignant bone tumor in children and adolescents, with a poor prognosis for metastatic disease. While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their efficacy in metastatic OSA is limited and highly variable, lacking clear predictive biomarkers.

Peripheral blood lymphocyte subsets, reflecting systemic immune status, show promise as non-invasive predictors of ICIs efficacy and patient prognosis, yet their dynamic changes and predictive value in metastatic OSA are largely unexplored.MethodsThis single-center, retrospective study included 14 metastatic OSA patients receiving ICIs. Peripheral blood lymphocyte subsets (CD3+, CD4+, CD8+ T cells, NK cells, and activated T cells like CD4+HLA-DR+, CD8+HLA-DR+) were quantified by flow cytometry at diagnosis, pre-ICIs, and post-ICIs.

Overall survival (OS) and treatment response (RECIST 1.1) were evaluated. Statistical analyses, including univariate Cox regression, group comparisons, and Linear Mixed Models (LMM), assessed the relationship between lymphocyte subsets, their dynamic changes, and clinical outcomes.ResultsUnivariate Cox regression identified pre-ICIs CD8+HLA-DR+ cells, and post-ICIs CD3−CD56+, CD3+CD4+, and CD8+HLA-DR+ cells as protective factors for OS.