INTEGRATED EFFICACY AND SAFETY ANALYSIS OF LETETRESGENE AUTOLEUCEL, A T-CELL RECEPTOR T-CELL THERAPY, ACROSS CLINICAL TRIALS OF PATIENTS WITH SYNOVIAL SARCOMA AND MYXOID/ROUND CELL LIPOSARCOMA

unified cohort of 134 patients was formed using tissue microarrays from two sarcoma centers: 109 cases from MD Anderson Cancer Center and 25 from Fred Hutchinson Cancer Center (FHCC).Two mIHC panels were used: CD4, CD68/CD163, CD8, FoxP3, PD-1, PD-L1 (with post-mIHC ERG DAB) and CD68, CD20, CD3, CD163, CD206, CD34.Transcriptomic analysis was performed using the NanoString IO 360 panel on 25 angiosarcoma samples from FHCC with 9 hemangiomas as controls. Results:We observed significant differences in immune cell infiltration between cutaneous and non-cutaneous angiosarcomas, with higher levels of CD20+ B-cells (p=0.015),CD3+ T-cells (p=0.007),CD8+ T-cells (p< 0.001), FOXP3+ regulatory Tcells (p< 0.001), PD1+ cells (p=0.004) and CD4+ T-cells (p=0.015) in cutaneous tumors.Survival analysis demonstrated that higher CD20+ B-cell infiltration was significantly associated with improved overall survival (p=0.014).Gene expression analysis revealed higher MAPK pathway-related transcripts including MAP4K2 and MAPKAPK2 in angiosarcomas.Angiosarcomas also had higher complement levels (C5/C6), and lower expression of interleukin 1 receptor antagonist (IL1RN).When comparing angiosarcoma subtypes, scalp/face tumors showed distinctive immune profiles with lower complement expression and higher expression of inflammatory markers S100A8, S100A9, NOD2, and IL1B; paired with higher CD3+ and CD4+ cell infiltration on mIHC compared to other sites. Conclusion:These findings provide insights into the immunological landscape of angiosarcomas across different anatomical locations.The significantly higher immune infiltration in cutaneous versus non-cutaneous angiosarcomas suggests distinct immunological mechanisms, consistent with higher immunotherapy responsiveness in cutaneous angiosarcomas.Our results suggest that immune cell infiltration, particularly CD20+ B-cells, may serve as prognostic biomarkers in this rare disease.