TY  - EJOU
AU  - Kokkali, Stefania 
AU  - Sarantis, Panagiotis 
AU  - Tsakirakis, Nikolaos 
AU  - Anastasiou, Ioanna A. 
AU  - Keratsa, Panoraia 
AU  - Arnogiannaki, Niki 
AU  - Kyriazoglou, Anastasios 
AU  - Vourlakou, Christina 
AU  - Simopoulou, Sophia 
AU  - Karamouzis, Michail 
AU  - Tsitsilonis, Ourania 
AU  - Theocharis, Stamatios 

TI  - Immune Checkpoint Blockade in Soft Tissue Sarcoma: Treatment Efficacy and Biomarker Exploration
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Objectives:</b> The effectiveness of immune checkpoint inhibitors (ICIs) in soft tissue sarcomas (STS) is still under investigation. The present study aimed to explore the activity of atezolizumab in combination with different chemotherapeutic drugs in leiomyosarcoma (LMS) and liposarcoma (LPS) cell lines. <b>Methods:</b> The immune cell composition in tumors and the peripheral blood from STS patients who received ICIs was analyzed. LMS HTB-88 cells and LPS HTB-92 cells were co-cultured with Peripheral Blood Mononuclear Cells (PBMCs) to establish 3D cell cultures. Cell viability was assessed with the methyl-thiazol-tetrazolium assay. Flow cytometry was used to assess the frequency of peripheral blood mononuclear cell subsets in five STS patients. Baseline formalin-fixed paraffin-embedded tumor specimens from n = 9 patients who received off-label ICIs were used for an immunohistochemical study of the tumor microenvironment. <b>Results:</b> Atezolizumab significantly reduced cell viability in both cell lines when combined with single-agent chemotherapies, suggesting an enhanced inhibitory effect. A consistent pattern of decreased cell viability was observed when atezolizumab was added to chemotherapy doublets. Peripheral blood immunophenotyping of STS patients revealed that patients with mixed response to ICIs showed higher natural killer and lower natural killer T cells (NKT) and regulatory T cell pre-treatment levels, compared to nonresponders. Tumor samples from responders exhibited cluster of differentiation 20 (CD20) + B-cell infiltration. <b>Conclusions:</b> Atezolizumab in combination with chemotherapies has demonstrated promising results and therefore warrants further evaluation in clinical trials involving LMS and LPS patients. Moreover, immune cell infiltration within tumors, as well as distinct immune cell patterns in the peripheral blood at treatment initiation, could serve as biomarkers of response to ICIs.
KW  - Immunotherapy; immune checkpoint inhibitor; leiomyosarcoma; liposarcoma; soft tissue sarcoma; flow cytometry; immunotherapy biomarker

DO  - 10.32604/or.2026.082480