Association of circulating T cell and tumor microenvironment profiles with immune checkpoint blockade outcomes in sarcoma: pooled analysis

Immune checkpoint blockade (ICB) benefits only a subset of patients with sarcoma. Biomarkers of response and resistance are needed to help guide patient selection. Pooled analysis of five ICB-based clinical trials evaluated the association of circulating T cell and tumor microenvironment (TME) profiles with ICB outcomes in sarcoma. Among 178 patients with peripheral blood mononuclear cells (PBMC) data available for analysis, a proliferative (PRO) circulating T-cell immunotype was associated with poorer overall survival (OS) than lymphocyte-activation gene 3 (LAG)-negative or LAG-positive immunotypes. RNA sequencing from 67 tumors identified an immune-enriched/nonfibrotic TME subtype associated with a higher response rate, longer progression-free survival, and longer OS compared with immune-enriched/fibrotic, immune-depletd, and fibrotic subtypes. Automated analysis of 48 baseline H&E slides identified lymphoid aggregates in five tumors: four were classified as immune-enriched, and two of these responded to ICB. The authors conclude that these findings support the use of a multimodel approach to identify predictors of response to ICB in sarcoma.