Immune Modulation in Sarcoma: Targeting the Tumor Microenvironment

Introduction

Sarcomas are a varied group of mesenchymal neoplasms that can impact a range of tissues, including bone, cartilage, muscle, nerves, and connective tissues.¹ They include soft tissue sarcomas (STS) such as malignant fibrous histiocytoma, liposarcoma, and leiomyosarcoma, as well as primary bone sarcomas like osteosarcoma, Ewing sarcoma, giant cell tumor, and chondrosarcoma.²

STS have been further categorized into subtypes according to the NCCN classification, including STS of extremity, superficial/trunk, or head and neck; retroperitoneal or intra-abdominal STS; desmoid tumors (aggressive fibromatosis); and rhabdomyosarcoma, to facilitate management.³ Seth M. Pollack, MD, professor at the Feinberg School of Medicine at Northwestern Medicine, gave a lecture at the MedNews Week Keynote Conference focusing on these rare cancers, comprising 1% of all adult malignancies and leading to 5130 deaths in 2022 alone.^1,3 The primary sites of STS origin are the extremities (43%), the trunk (10%), viscera (19%), retroperitoneum (15%), and the head and neck (9%).³ The pelvis is the most common site of origin for bone sarcomas, followed by the proximal femur, proximal humerus, distal femur, and ribs.³

Though traditionally sarcomas have been classified based on morphology and type of tissue they resemble, in recent years they have been classified based on the genetic alteration into sarcomas with specific genetic alterations and sarcomas with complex aneuploidy karyotypes, consisting of numerous losses, gains, and amplifications.⁴ Pollack brings to light another important classification of sarcomas for the tumor response and clinical efficacy. When categorizing tumors into hot, cold, and variable types, various factors are taken into consideration. This includes details about the cancer cells, the immune characteristics of the tumor, the microenvironment in which the tumor is situated, and the signaling mechanisms involved.⁵ These factors all play a significant role in determining the classification of tumors. Understanding the immunobiology of these tumors is crucial for the effective application of immunotherapy. This classification is centered on the delicate balance between the tumor’s ability to evade the immune system and the immune system’s coordination and response to the tumor.⁵

This unique immunobiology provides a promising opportunity for the use of immunotherapy. Immunotherapy is a type of treatment that focuses on harnessing the body’s own immune system to target and destroy tumors.⁵ It works by reactivating and maintaining the immune response against the tumor as well as enhancing the body’s natural ability to fight against cancer.

In this paper, Pollack’s lecture is discussed, and the authors explore the normal tumor microenvironment (TME) and how differences in TME can alter tumor response and patient outcomes. The authors also look at the potential effects of radiation therapy on the TME. Pollack delves into the intricacies of altering the TME to effectively treat sarcomas. Strategies for overcoming TME inhibitory macrophages are investigated to enhance patient outcomes. This is especially important for patients with poor outcomes and involves the implementation of several precision techniques, including immunotherapy (such as T-cell receptor [TCR] therapy, cancer testis antigen [CTA]-targeting cells, and chimeric antigen receptor [CAR] T-cell therapy) and neoadjuvant therapy in combination with radiation treatment (Figure).

The Role of the TME and Immune Modulation in Sarcoma Therapy

Sarcoma cells continually interact with their TME, which includes various cellular (tumor-infiltrating lymphocytes, tumor-associated macrophages, dendritic cells, myeloid-derived suppressor cells, and natural killer [NK] cells) and noncellular (vascular beds and extracellular matrix) components.⁶ This interaction influences tumor progression and response to treatment. The TME often suppresses antitumor activity, indicated by the scarcity of CD8+ T cells, high levels of immunosuppressive cytokines (TGF-β and IL-10), and an abundance of regulatory T cells (Tregs) and CD206+ macrophages.⁶ Continuous exposure of T cells to tumor antigens leads to exhaustion, reducing their cytotoxic abilities and proliferation, and expressing multiple inhibitory receptors such as PD-1, TIM-3, and LAG-3.⁷ Inhibitory T-cell immune checkpoint receptors like PD-1, when interacting with PD-L1, inhibit T-cell function, predicting responses to immune checkpoint inhibitors (ICIs).^8,9 Tregs produce immunosuppressive cytokines (IL-10, TGF-β), express coinhibitory molecules (CTLA-4, PD-1, PD-L1), and capture IL-2, inhibiting T-cell responses and promoting tumor immune escape.⁷

Not all sarcomas have the same TME composition; some are cold tumors with low tumor mutational burden and PD-L1 expression.⁹ The TME’s composition and behavior are determined by the genetic makeup of the sarcoma.⁶ Pollack’s paper “T-Cell Infiltration and Clonality Correlate With Programmed Cell Death Protein 1 and Programmed Death-Ligand 1 Expression in Patients With Soft Tissue Sarcomas” examines the TME in various STS, from simple genetic alterations like liposarcomas and synovial sarcoma to highly mutated complex alterations like undifferentiated pleomorphic sarcomas (UPS) and leiomyosarcoma.^8,10The study assessed 760 genes using a NanoString platform, examined PD-1 and PD-L1 expression with immunohistochemistry, and analyzed TCR diversity and clonality using TCR-Vβ sequencing.⁹

The study found that STS with complex mutations like UPS have higher PD-1/PD-L1 expression, more T-cell infiltration, higher clonality, and better responses to PD-L1 inhibitors.^8,10 This is attributed to complex genetic mutations creating neoantigens that are immunogenic targets for T cells, potentially inhibited by ICIs.^10,11 Higher tumor mutational burden increases the likelihood of ICI efficacy. Despite high T-cell infiltration and PD-1/PD-L1 staining, leiomyosarcoma responds poorly to checkpoint inhibitors.^8,10 STS with simple mutations, like synovial sarcoma and mixed round-cell liposarcoma, show lower PD-L1 expression, fewer T-cell infiltration markers (CD3D, IL-7 receptor), fewer MHC molecules (HLA-A, HLA-DP), lower clonality, and limited responses to checkpoint inhibitors.^8,10

TCR sequencing identifies TCR diversity and clonality, with high clonality indicating a focused immune response and low clonality suggesting a less targeted response.¹² Liposarcomas provided unexpected results; dedifferentiated liposarcomas showed high clonality and low fractions associated with worse outcomes.^8,10 Further examination identified favorable markers like B cells and CD4, while macrophages and CD14+ monocytes were linked to poorer outcomes.^8,10 Macrophages, both inflammatory (M1) and inhibitory (M2), are critical in the TME of sarcomas, with inhibitory macrophages linked to poorer outcomes in tumors like leiomyosarcoma.^8,10

Pollack also discusses the impact of radiation therapy on the TME postneoadjuvant therapy, noting an upregulation of genes related to antigen presentation, B cells, NK cells, and macrophage markers.^8,13 While radiation is crucial for tumor control, it increases inhibitory macrophage populations, complicating treatment.^8,13

Enhancing Antitumor Immune Responses in Sarcoma Through Targeted Modulation of the TME

Recently, a study on the TME of patients with sarcoma, specifically before and after neoadjuvant therapy, showed that the immune landscape post therapy had significant changes. This was mainly characterized by the increase in antigen presentation molecules such as HLA-DR, B cells, and NK cells, accompanied by an upregulation in gene expression related to antigen presentation and a notable rise in macrophage-related markers.¹⁴ While radiation therapy is considered necessary for tumor suppression/control, it was found to potentially increase the number of inhibitory macrophages within the TME.¹⁵

To counteract the difficulty posed by inhibitory macrophages, the study investigated the use of toll-like receptor (TLR) agonists, specifically a TLR4 agonist, GLA, in combination with radiation therapy. This strategy aimed at converting inhibitory macrophages into activating macrophages, hence increasing the antitumor response.¹⁶ Results among patients with metastatic sarcoma in the phase 1 trial (NCT02180698) showed that tumors injected with the TLR4 agonist exhibited better responses than the ones treated with radiation. This suggests that TLR4 activation may enhance the effects of radiation by modifying the macrophage phenotype.¹⁷

Surprisingly, the TLR4 agonist was not found to be associated with the TLR4 expression directly on tumor cells but rather with the activation of immune cells within the TME, which aligns with previous studies done in hematologic malignancies where TLR activation targeted immune cells rather than tumor cells.¹⁸ The patients who demonstrated strong local reactions to the combined therapy displayed elevated T-cell infiltration and clonal expansion, with
single-cell sequencing disclosing a Th1 phenotype in expanded T-cell clones. This signifies a strong antitumor immune response. The posttreatment rise in peripheral blood mononuclear cell clonalities among those who responded also suggests systemic immune activation.¹⁹

Additional inquiries into the matter looked at the potential of using trabectedin, along with ICIs such as pembrolizumab, to regulate macrophage activity throughout the body. Trabectedin is a substance that can effectively eliminate macrophages within tumors. It demonstrated encouraging findings among patients displaying a high M2 macrophage gene signature, indicating its double effect on both tumor cells and macrophages.²⁰ The mixture of trabectedin and ICIs showed better progression-free survival and overall survival in patients with liposarcoma or leiomyosarcoma. The fact that higher T-cell clonalities before treatment relate to improved responses, therefore, highlights how crucial it is for an enhanced immune environment before therapy success.²¹

In conclusion, the study highlights the intricate interplay between the immune landscape, therapeutic interventions, and tumor responses in patients with sarcoma. By targeting inhibitory macrophages through TLR4 agonists and trabectedin-based strategies, researchers aim to enhance antitumor immune responses and improve treatment outcomes in patients with sarcoma.

Targeting Cancer Testis Antigens in Sarcoma Immunotherapy

In the field of sarcoma immunotherapy, tumors expressing high levels of cancer testis antigens (CTAs) can be effectively targeted. CTAs are typically expressed at high levels in the testis, specifically in immature sperm cells located at the periphery of the seminiferous tubules, while mature sperm reside in the center. Notably, fetal organs like the fetal ovary and placenta also exhibit high CTA expression, whereas healthy tissues in children and adults, excluding the testis and placenta, do not. This makes CTAs, such as NY-ESO-1, promising targets for cancer therapies.

Pollack’s research on synovial sarcoma revealed that all observed cases expressed NY-ESO-1, with approximately 70% showing homogeneous expression of NY-ESO-1 and other CTAs in both synovial sarcoma and myxoid/round cell liposarcoma. Although rare patients may lack NY-ESO-1 or MAGE family antigens, these findings support the potential of CTA-targeted therapies.

CAR T cells and gene-engineered TCR T cells are central to this discussion. CAR T cells, which are FDA approved for acute lymphoblastic leukemia, leukemia, and lymphoma, target specific cell surface proteins using CD19-specific and CD20-specific constructs. These cells incorporate an SEF from an antibody, linked to molecules such as CD28 or 4-1BB, and a CD3ζ chain to activate the T cell upon target recognition. In contrast, TCR T cells identify intracellular proteins presented on the cell surface by MHC molecules, requiring specific HLA types, such as HLA-A0201. TCRs can be developed for various HLA types, though this process is costly and complex.

In this study, Pollack cultured NY-ESO-1–specific T cells from patients’ blood. Dendritic cells pulsed with NY-ESO-1 peptide produced a population of NY-ESO-1–specific T cells, which were then used to stimulate the patients’ blood, yielding purified T-cell products for treatment.²²

A pilot study on IL-15–mediated expansion of memory T cells following adoptive cellular therapy with cyclophosphamide conditioning showed clinical benefits such as stable disease and reduction in liver and lung lesions, though progression eventually occurred.²³ Sequencing revealed these T cells retained activity but lacked markers of activation and cytokine production.

Additionally, tumors with low HLA expression pose challenges. Pollack’s team explored interferon gamma to enhance MHC and T-cell presence in tumors.²⁴

A pilot study demonstrated increased class I expression in over half of the patients, with some developing NY-ESO-1–specific T-cell responses.²⁵ However, a PD-1 inhibitor trial with interferon gamma showed no response, necessitating further research.

Interferon gamma combined with cellular therapy indicated technical progression in some patients, reducing symptoms and expressing NY-ESO-1, though class I MHC was not expressed.²⁶ A second trial was halted due to fatal myocarditis in patients with advanced synovial sarcomas.

Approved therapies, such as MAGE-A4 TCR therapy, are under development. Additionally, sarcomas in pet dogs, similar to human sarcomas, led Pollack’s team to create a canine CAR T cell, potentially improving cellular therapy.²⁷

Another study highlighted TME reprogramming via ketotifen, enhancing nanomedicine-based chemoimmunotherapy in sarcomas.²⁸ Ketotifen reduced tumor stiffness, increased perfusion, and improved therapeutic efficacy when combined with anti–PD-1 and alendronate. This combination increased cytotoxic CD8+ and CD4+T-cell infiltration and decreased regulatory T cells, disrupting tumor-associated macrophage polarization. These findings underscore the potential of ketotifen-induced TME reprogramming to boost nanomedicine-based chemoimmunotherapy efficacy in sarcomas.

The study highlights the potential of targeting CTAs in sarcoma immunotherapy, with NY-ESO-1 being a particularly favorable target. CAR T cells and TCR T cells offer innovative approaches, though challenges such as low HLA expression and inhibitory TME remain. Combining therapies like interferon gamma and ketotifen with cellular and ICIs shows promise in enhancing antitumor responses and improving patient outcomes. The ongoing development of new therapies, including those for canine sarcomas, highlights the dynamic nature of research in this field.

New Developments in Sarcoma Immunotherapy

Since the original lecture referenced in this paper, there have been notable advancements in the field of sarcoma immunotherapy. A key update is the approval of afamitresgene autoleucel, a TCR therapy, for synovial sarcoma, which was officially approved in August 2024. This approval marks a significant milestone in treatment options for this challenging sarcoma subtype, which previously lacked effective immunotherapeutic options. The approval is based on promising clinical data showing improved patient outcomes with afamitresgene autoleucel, offering hope for a more personalized and targeted approach to therapy.²⁹ Therefore, TCR therapy is no longer just a promising treatment but a recognized and approved option for patients with synovial sarcoma. This development significantly impacts the landscape of sarcoma treatment, and it is essential for health care providers to stay informed about these advancements to guide clinical decisions.

Additionally, recent data presented at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting have further expanded our understanding of the TME and its role in modulating immune responses in sarcoma treatment. One important study shared at CTOS, the phase 2 EFTISARC-NEO trial (NCT06128863), has examined the effects of radiation therapy combined with trabectedin chemotherapy in patients with advanced sarcomas. Preliminary results from this trial suggest significant improvements in treatment efficacy, highlighting the potential benefits of this combination therapy in modulating the TME.³⁰ The results underscore the importance of continuing to explore strategies that target both the tumor and its surrounding immune microenvironment, offering a potential avenue for improving patient outcomes and advancing the field of sarcoma therapy. These new data align with the growing body of research emphasizing the crucial role of TME modulation in sarcoma treatment, especially when combined with targeted therapies and immunotherapies.

Conclusions

Pollack’s keynote emphasized the importance of continuous learning and adaptation to stay ahead in the ever-evolving field of medicine. Effective immunotherapy, crucial for classification based on genetic alterations and tumor response, includes techniques like TCR therapy, CTA-targeting cells, and CAR T-cell therapy, which have shown results in clinical trials, offering new hope for patients with difficult-to-treat cancers. Health care professionals must stay informed about these advancements to provide the best possible care. A study on patients with sarcoma TME revealed significant changes in the immune landscape post therapy, including increased antigen presentation molecules, gene expression, and macrophage-related markers. Radiation therapy may increase inhibitory macrophages, counteracted by TLR agonists like GLA. Combining trabectedin and ICIs can improve progression-free survival. Targeting CTAs, characterized by high expression in the testis, is effective in immunotherapy for sarcomas, with CAR T cells, FDA approved for various cancers, being used to target synovial sarcomas.

Overall, immunotherapy has shown optimistic results in treating sarcomas by targeting specific antigens, utilizing CAR T cells, and enhancing the immune response against cancer cells. The recent approval of TCR therapy further expands the options for targeting tumor-specific antigens, offering hope for patients who may not respond to traditional treatments. Combining different therapeutic approaches, such as radiation therapy and ICIs, can enhance treatment effectiveness and improve patient outcomes. Ongoing research explores the potential of combining various immunotherapeutic approaches to further improve outcomes for patients with sarcomas. These advancements in immunotherapy offer new hope for patients, providing alternative options for those who may not respond well to traditional treatments. By targeting specific antigens and enhancing the immune system’s ability to recognize and attack cancer cells, immunotherapy is revolutionizing the approach to this rare type of cancer. With more continued research and clinical trials, the future of sarcoma treatment has potential, leading to more effective and personalized therapies for patients in the years to come.

Author Contributions

Conceptualization, JG and HV; methodology, JG and HV; formal analysis, JG, HV, VC, AHA, KI, YL, CHP, and KB; investigation, JG, HV, VC, AHA, KI, YL, CHP, JG, HV, VC, AHA, KI, YL, and CHP; data curation, JG, HV, VC, AHA, KI, YL, and CHP; writing—original draft preparation, JG, HV, VC, AHA, KI, YL, and CHP; writing—review and editing, JG and HV; visualization, JG, HV, VC, AHA, KI, YL, and CHP; supervision, JG and HV; project administration, JG, HV, CHP, and YL. All authors jointly agree on the accuracy of this work and are in favor of submitting it for publication. All authors have read and agreed to the published version of the manuscript.

Acknowledgments

We thank Seth M. Pollack, MD, for the opportunity to learn from a global leader in medicine. We are grateful to be part of MedNews Week. We would like to express our sincere gratitude to Jill Gregory for her invaluable assistance in significantly improving the figures of this manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

References

1. Bleloch JS, Ballim RD, Kimani S, et al. Managing sarcoma: where have we come from and where are we going? Ther Adv Med Oncol. 2017;9(10):637-659. doi:10.1177/1758834017728927
2. Skubitz KM, D’Adamo DR. Sarcoma. Mayo Clin Proc. 2007;82(11):1409-1432. doi:10.4065/82.11.1409
3. von Mehren M, Kane JM, Agulnik M, et al. Soft tissue sarcoma, version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(7):815-833. doi:10.6004/jnccn.2022.0035
4. Jain S, Xu R, Prieto VG, Lee P. Molecular classification of soft tissue sarcomas and its clinical applications. Int J Clin Exp Pathol. 2010;3(4):416-428.
5. Wang L, Geng H, Liu Y, et al. Hot and cold tumors: immunological features and the therapeutic strategies. MedComm (2020). 2023;4(5):e343. doi:10.1002/mco2.343
6. Jumaniyazova E, Lokhonina A, Dzhalilova D, Kosyreva A, Fatkhudinov T. Immune cells in the tumor microenvironment of soft tissue sarcomas. Cancers (Basel). 2023;15(24):5760. doi:10.3390/cancers15245760
7. Ando M, Ito M, Srirat T, Kondo T, Yoshimura A. Memory T cell, exhaustion, and tumor immunity. Immunol Med. 2020,43(1):1-9. doi:10.1080/25785826.2019.1698261
8. Pollack SM. Altering the sarcoma immune microenvironment for effective therapy. Presented at: MedNews Week Keynote Conference;May 27, 2023. Accessed February 2025. Videocast available at: https://tinyurl.com/2nr64mvu
9. Anastasiou M, Kyriazoglou A, Kotsantis I, et al. Immune checkpoint inhibitors in sarcomas: a systematic review. Immunooncol Technol. 2023;20:100407. doi:10.1016/j.iotech.2023.100407
10. Pollack SM, He Q, Yearley JH, et al. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer. 2017;123(17):3291-3304. doi:10.1002/cncr.30726
11. Yi M, Qin S, Zhao W, Yu S, Chu Q, Wu K. The role of neoantigen in immune checkpoint blockade therapy. Exp Hematol Oncol. 2018;7:28. doi:10.1186/s40164-018-0120-y
12. Aran A, Garrigós L, Curigliano G, Cortés J, Martí M. Evaluation of the TCR repertoire as a predictive and prognostic biomarker in cancer: diversity or clonality? Cancers (Basel). 2022;14(7):1771. doi:10.3390/cancers14071771
13. Goff PH, Riolobos L, LaFleur BJ, et al. Neoadjuvant therapy induces a potent immune response to sarcoma, dominated by myeloid and B cells. Clin Cancer Res. 2022;28(8):1701-1711. doi:10.1158/1078-0432.CCR-21-4239
14. Smith C, Corvino D, Beagley L, et al. T cell repertoire remodeling following post-transplant T cell therapy coincides with clinical response. J Clin Invest. 2019;129(11):5020-5032. doi:10.1172/JCI128323
15. Anagnostou V, Smith KN, Forde PM, et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 2017;7(3):264-276. doi:10.1158/2159-8290.CD-16-0828
16. Achard C, Surendran A, Wedge ME, Ungerechts G, Bell J, Ilkow CS. Lighting a fire in the tumor microenvironment using oncolytic immunotherapy. EBioMedicine. 2018;31:17-24. doi:10.1016/j.ebiom.2018.04.020
17. Seo YD, Lu H, Black G, et al. Toll-like receptor 4 agonist injection with concurrent radiotherapy in patients with metastatic soft tissue sarcoma: a phase 1 nonrandomized controlled trial. JAMA Oncol. 2023;9(12):1660-1668. doi:10.1001/jamaoncol.2023.4015
18. Simon Davis DA, Mun S, Smith JM, et al. Machine learning predicts cancer subtypes and progression from blood immune signatures. PLoS One. 2022;17(2):e0264631. doi:10.1371/journal.pone.0264631
19. Caushi JX, Zhang J, Ji Z, et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature. 2021;596(7870):126-132. doi:10.1038/s41586-021-03752-4
20. Kyi C, Postow MA. Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges. Immunotherapy. 2016;8(7):821-837. doi:10.2217/imt-2016-0002
21. Leng D, Yang Z, Sun H, et al. Comprehensive analysis of tumor microenvironment reveals prognostic ceRNA network related to immune infiltration in sarcoma. Clin Cancer Res. 2023;29(19):3986-4001. doi:10.1158/1078-0432.CCR-22-3396
22. Jungbluth AA, Chen YT, Stockert E, et al. Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues. Int J Cancer. 2001;92(6):856-860. doi:10.1002/ijc.1282
23. Kohli K, Yao L, Nowicki TS, et al. IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy. J Immunother Cancer. 2021;9(5):e002232. doi:10.1136/jitc-2020-002232
24. Mitchell G, Pollack SM, Wagner MJ. Targeting cancer testis antigens in synovial sarcoma. J Immunother Cancer. 2021;9(6):e002072. doi:10.1136/jitc-2020-002072
25. Zhang S, Kohli K, Black RG, et al. Systemic interferon-γ increases MHC class I expression and T-cell infiltration in cold tumors: results of a phase 0 clinical trial. Cancer Immunol Res. 2019;7(8):1237-1243. doi:10.1158/2326-6066.CIR-18-0940
26. Schroeder BA, Black RG, Spadinger S, et al. Histiocyte predominant myocarditis resulting from the addition of interferon gamma to cyclophosphamide-based lymphodepletion for adoptive cellular therapy. J Immunother Cancer. 2020;8(1):e000247. doi:10.1136/jitc-2019-000247
27. Zhang S, Black RG, Kohli K, et al. B7-H3 specific CAR T cells for the naturally occurring, spontaneous canine sarcoma model. Mol Cancer Ther. 2022;21(6):999-1009. doi:10.1158/1535-7163.MCT-21-0726
28. Charalambous A, Mpekris F, Panagi M, et al. Tumor microenvironment reprogramming improves nanomedicine-based chemo-immunotherapy in sarcomas. Mol Cancer Ther. 2024;23(11):1555-1567. doi:10.1158/1535-7163.MCT-23-0772
29. Winstead E. FDA approves engineered cell therapy for advanced synovial sarcoma. National Cancer Institute. August 27, 2024. Accessed March 20, 2025. https://tinyurl.com/39nfmdch
30. Sobczuk P, Rogala P, Mariuk-Jarema A, et al. Preliminary results from the phase 2 EFTISARC-NEO trial of neoadjuvant soluble LAG-3 protein eftilagimod alpha, pembrolizumab, and concurrent radiotherapy in patients with resectable soft tissue sarcoma. Presented at: Connective Tissue Oncology Society 2024 Annual Meeting; November 13-16, 2024; San Diego, CA.