(P 104) COMPREHENSIVE IMMUNE PROFILING UNVEILS A SUBSET OF LEIOMYOSARCOMA WITH HOT TUMOR IMMUNE MICROENVIRONMENT

Objective: To investigate the immune biomarker in Leiomyosarcoma (LMS) which is a rare and recognized as an “immune-cold” cancer showing a poor response rate ( < 10%) to immune checkpoint inhibitors (ICIs). However, durable response and clinical benefit to ICIs observed in few LMS, including, but not only, LMS with tertiary lymphoid structure (TLS) structures.

Methods: We used comprehensive transcriptomic profiling and a deconvolution method extracted from RNA-sequencing gene expression data in two independent LMS cohorts, the International Cancer Genome Consortium (ICGC, N=146) and The Cancer Genome Atlas (TCGA, N=75) to explore tumor immune microenvironment (TIME) in LMS.

Results: Unsupervised clustering analysis using the previously validated two methods-- 90 gene signature and the Cell-type Identification By Estimating Relative Subsets of RNA Transcripts (CIBERSORT), identified immune hot (I-H) and immune high (I-Hi) LMS respectively in ICGC cohort. Similarly, immune active groups (T-H, T-Hi) were identified in TCGA cohort using these two methods. These immune active (“hot”) clusters were significantly associated, but not completely overlapping, with several validated immune signatures such as sarcoma immune class (SIC) classification and TLS score, T cell inflamed signature (TIS) score, immune infiltration score (IIS), and macrophage score (M1/M2), with more patients identified by our clustering as potentially immune hot.

Conclusion: Comprehensive immune profiling revealed a subset of LMS with a distinct active ("hot”) TIME, consistently associated with several validated immune signatures in other cancers. This suggests that the methodologies that we used in this study warrant further validation and development, which can potentially help refine our current immune biomarkers to select the right LMS patients for ICIs in clinical trials.

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