35P - Peripheral immunotype classification for monitoring Soft Tissue Sarcoma patients

Background

Current immune research on soft tissue sarcomas (STS) primarily focuses on analyzing the tumor microenvironment and adjacent lymph nodes. However, alternative methods are necessary to monitor immune responses in non-surgical patients due to limited opportunities to study tumor-infiltrating lymphocytes. This study aimed to assess the peripheral immune profile of STS patients and its impact on patient survival.

Methods

Blood samples were collected from 55 STS patients and age-matched healthy individuals. Flow cytometry and qRT-PCR were conducted on whole blood, to proceed with deep immunophenotyping and gene expression quantification, respectively. Proteomic analysis was also performed on plasma samples by xMAP technology. Unsupervised clustering analysis was used to classify patients based on their immunotype.

Results

Significant differences were found between STS patients and healthy individuals. STS patients showed lymphopenia, particularly affecting B and CD4 T cells, with an expansion of myeloid cells such as granulocytes and monocytic-derived suppressor cells (M-MDSC). Gene expression analysis revealed decreased levels of activatory and cytotoxic-related factors, along with increased expression of ARG1, which may inhibit anti-tumoral activity. A tendency for increased levels of IL-10 and soluble checkpoint inhibitors VISTA and TIMD-4 were also observed in plasma samples. Furthermore, patients were classified into three distinct immunotypes: \"immune-high,\" \"immune-intermediate,\" and \"immune-low.\" These immunotypes correlated significantly with time after collection (TAC), which refers to the time from sample collection to the end of the study or occurrence of a death event. \"Immune-high\" patients had elevated levels of immune-related factors associated with cytotoxic/effector activity and longer TAC, while \"immune-low\" patients had increased levels of immune-related factors associated with inflammation and inhibition, and shorter TAC.

Conclusions

The correlation between immunotypes and survival times emphasizes the importance of studying peripheral blood samples in STS. Evaluating the peripheral immune response can be a valuable tool for monitoring and predicting outcomes in STS patients.

Legal entity responsible for the study

The authors.

Funding

FCT - Portuguese Foundation for Science and Technology.

Disclosure

All authors have declared no conflicts of interest.