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ARTICLE

Immune Checkpoint Blockade in Soft Tissue Sarcoma: Treatment Efficacy and Biomarker Exploration

Stefania Kokkali1,2,*, Panagiotis Sarantis3, Nikolaos Tsakirakis4, Ioanna A. Anastasiou5, Panoraia Keratsa1, Niki Arnogiannaki6, Anastasios Kyriazoglou7, Christina Vourlakou8, Sophia Simopoulou6, Michail Karamouzis9, Ourania Tsitsilonis4, Stamatios Theocharis2
1 Oncology Unit, 2nd Department of Medicine, Medical School, National and Kapodistrian University of Athens, Hippocratio General Hospital of Athens, Athens, Greece
2 First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
3 Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
4 Flow Cytometry Unit, Department of Biology, School of Science, National and Kapodistrian University of Athens, Athens, Greece
5 Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
6 Department of Pathology, St Savvas Cancer Hospital, Athens, Greece
7 Oncology Unit, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece
8 Department of Pathology, Evangelismos Hospital, Athens, Greece
9 Academic Department of Internal Medicine, General and Oncology Hospital “Agioi Anargyroi”, National and Kapodistrian University of Athens, Kifisia, Greece
* Corresponding Author: Stefania Kokkali. Email: email

Oncology Research https://doi.org/10.32604/or.2026.082480

Received 17 March 2026; Accepted 24 July 2026; Published online 26 August 2026

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Graphical Abstract

Immune Checkpoint Blockade in Soft Tissue Sarcoma: Treatment Efficacy and Biomarker Exploration

Keywords

Immunotherapy; immune checkpoint inhibitor; leiomyosarcoma; liposarcoma; soft tissue sarcoma; flow cytometry; immunotherapy biomarker

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