36P - Expression of germinal center B cell- and Th17 cell-related transcripts are prognostic of soft-tissue sarcoma patient outcomes

Background

Soft tissue sarcomas (STS) are a group of rare and heterogeneous tumors with different clinical and biological behaviors. Better prognosis has been associated to an inflamed tumor microenvironment (TME) characterized by the presence of tertiary lymphoid structures (TLSs) rich in B cells. However, studies are still needed to better characterize cellular and molecular components of the TME the that could favor or hamper B cell organization in STS-associated TLSs.

Methods

The transcriptomic immune profiling of STS TME was performed using the Human Immunology V2 Panel and the NanoString nCounter platform on 33 STS biopsies or surgical samples. Patients with primary or locally recurrent STS were enrolled and treated at the Careggi Hospital (Florence, Italy; RESEARCH study). Results were validated by retrieving RNA-sequencing and clinical data for 164 STS patients from The Cancer Genome Atlas (TCGA) SARC project.

Results

We investigated the impact of gene signatures discriminating for specific immune cells and we found a significant association with relapse-free survival (RFS) only for germinal center (GC) B cell- and T helper 17 (Th17) cell-related signatures (p < 0.05). We observed a correlation between GC-B and Th17 signatures (r = 0.77, p < 0.0001), and the combination of both GC B and Th17 signatures was associated with better RFS, while low expression of both GC B and Th17 signatures was associated with the worst survival outcome (p = 0.035). The prognostic value of the GC-B/Th17 signature was confirmed on data from TCGA SARC project for both RFS (p = 0.016) and overall survival (p = 0.014). Differential gene expression analysis showed a more inflamed landscape in GC-B/Th17-high tumors. Conversely, the upregulation of genes encoding immunosuppressive molecules and genes related to tumor-associated macrophages with an immunosuppressive phenotype, were observed in GC-B/Th17-low tumors.

Conclusions

Our data identified a novel prognostic signature composed of GC B cell- and Th17 cell-related genes for STS patients, and suggest a potential collaboration between GC B cells and Th17 cells in mediating antitumor immune responses and potentially TLS formation in STS.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.