{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:43:46Z","timestamp":1790549026295,"version":"4.1.0"},"reference-count":172,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 CA009599"],"award-info":[{"award-number":["T32 CA009599"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leiomyosarcoma SPORE Career Enhancement Program","award":["Fondation pour la Recherche M\u00e9dicale, and Fondation Nuovo-Soldati"],"award-info":[{"award-number":["Fondation pour la Recherche M\u00e9dicale, and Fondation Nuovo-Soldati"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, and DNA damage response pathways that may contribute to resistance against immune-checkpoint blockade monotherapy. The LMS immune microenvironment is highly infiltrated with tumor-associated macrophages and tumor-infiltrating lymphocytes, which may represent promising biomarkers. This review provides an overview of the clinical and pathologic behavior of both soft tissue and uterine LMS and summarizes the genomic and immune characteristics of these tumors and how they may provide opportunities for the development of biomarker-based immune therapies.<\/jats:p>","DOI":"10.3390\/cancers15072099","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T08:27:27Z","timestamp":1680251247000},"page":"2099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Targeting the Molecular and Immunologic Features of Leiomyosarcoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Brandon M.","family":"Cope","sequence":"first","affiliation":[{"name":"Department of Surgery, Keesler Medical Center, Biloxi, MS 39534, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond S.","family":"Traweek","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Lazcano","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Z.","family":"Keung","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Lazar","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"UTHealth Houston Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-0087","authenticated-orcid":false,"given":"Christina L.","family":"Roland","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-6759","authenticated-orcid":false,"given":"Elise F.","family":"Nassif","sequence":"additional","affiliation":[{"name":"Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1200\/EDBK_205423","article-title":"More Than 50 Subtypes of Soft Tissue Sarcoma: Paving the Path for Histology-Driven Treatments","volume":"38","author":"Katz","year":"2018","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_2","unstructured":"Howlader, N., Noone, A.M., Krapcho, M., Garshell, J., Neyman, N., Altekruse, S.F., Kosary, C.L., Yu, M., Ruhl, J., and Tatalovich, Z. (2010). SEER Cancer Statistics Review, 1975\u20132010."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1200\/JCO.2017.75.9845","article-title":"Soft Tissue and Uterine Leiomyosarcoma","volume":"36","author":"George","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/S1470-2045(09)70226-8","article-title":"Clinical management of uterine sarcomas","volume":"10","author":"Amant","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"694","DOI":"10.3109\/0284186X.2012.689111","article-title":"Diagnosis and treatment of sarcoma of the uterus. A review","volume":"51","author":"Abeler","year":"2012","journal-title":"Acta Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1111\/j.1365-2559.2011.04070.x","article-title":"Dedifferentiated leiomyosarcoma: Clinicopathological analysis of 18 cases","volume":"59","author":"Chen","year":"2011","journal-title":"Histopathology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/his.12466","article-title":"Progressive loss of myogenic differentiation in leiomyosarcoma has prognostic value","volume":"66","author":"Demicco","year":"2015","journal-title":"Histopathology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1365-2559.2005.02292.x","article-title":"Evaluation of biological potential of smooth muscle tumours","volume":"48","author":"Miettinen","year":"2006","journal-title":"Histopathology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.ejso.2004.03.002","article-title":"Prognostic factors in soft tissue leiomyosarcoma of the extremities: A retrospective analysis of 42 cases","volume":"30","author":"Massi","year":"2004","journal-title":"Eur. J. Surg. Oncol. (EJSO)"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/1097-0142(19920701)70:1<114::AID-CNCR2820700119>3.0.CO;2-U","article-title":"Soft tissue leiomyosarcoma. A population-based epidemiologic and prognostic study of 48 patients, including cellular dna content","volume":"70","author":"Gustafson","year":"1992","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100209","DOI":"10.1016\/j.esmoop.2021.100209","article-title":"A single-arm multicentre phase II trial of doxorubicin in combination with trabectedin in the first-line treatment for leiomyosarcoma with long-term follow-up and impact of cytoreductive surgery","volume":"6","author":"Pautier","year":"2021","journal-title":"ESMO Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/S1470-2045(22)00380-1","article-title":"Doxorubicin alone versus doxorubicin with trabectedin followed by trabectedin alone as first-line therapy for metastatic or unresectable leiomyosarcoma (LMS-04): A randomised, multicentre, open-label phase 3 trial","volume":"23","author":"Pautier","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1200\/JCO.1999.17.1.150","article-title":"Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: An analysis of 2,185 patients treated with anthracycline-containing first-line regimens\u2014A European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study","volume":"17","author":"Oosterhuis","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Savina, M., Le Cesne, A., Blay, J.-Y., Ray-Coquard, I., Mir, O., Toulmonde, M., Cousin, S., Terrier, P., Ranchere-Vince, D., and Meeus, P. (2017). Patterns of care and outcomes of patients with METAstatic soft tissue SARComa in a real-life setting: The METASARC observational study. BMC Med., 15.","DOI":"10.1186\/s12916-017-0831-7"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1001\/jamasurg.2015.4205","article-title":"Clinical Observations and Molecular Variables of Primary Vascular Leiomyosarcoma","volume":"151","author":"Roland","year":"2016","journal-title":"JAMA Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0090-8258(03)00137-9","article-title":"Retrospective review of 208 patients with leiomyosarcoma of the uterus: Prognostic indicators, surgical management, and adjuvant therapy","volume":"89","author":"Giuntoli","year":"2003","journal-title":"Gynecol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ygyno.2017.02.012","article-title":"Prognosis and treatment of uterine leiomyosarcoma: A National Cancer Database study","volume":"145","author":"Seagle","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/cncr.27942","article-title":"Adjuvant therapy for high-grade, uterus-limited leiomyosarcoma: Results of a phase 2 trial (SARC 005)","volume":"119","author":"Hensley","year":"2013","journal-title":"Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1093\/annonc\/mdx484","article-title":"Improved survival using specialized multidisciplinary board in sarcoma patients","volume":"28","author":"Blay","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1093\/annonc\/mdz170","article-title":"Surgery in reference centers improves survival of sarcoma patients: A nationwide study","volume":"30","author":"Blay","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1245\/s10434-019-07421-9","article-title":"Survival Benefit of the Surgical Management of Retroperitoneal Sarcoma in a Reference Center: A Nationwide Study of the French Sarcoma Group from the NetSarc Database","volume":"26","author":"Bonvalot","year":"2019","journal-title":"Ann. Surg. Oncol."},{"key":"ref_22","unstructured":"National Comprehensive Cancer Network (2022). Soft Tissue Sarcoma (Version 2.2022), National Comprehensive Cancer Network."},{"key":"ref_23","unstructured":"National Comprehensive Cancer Network (2022). Uterine Neoplasms (Version 2.2022), National Comprehensive Cancer Network."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"ESMO\/European Sarcoma Network Working Group (2012). Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow. Ann. Oncol., 23, vii92\u2013vii99.","DOI":"10.1093\/annonc\/mds253"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1007\/s11912-000-0103-z","article-title":"Adjuvant chemotherapy for extremity soft-tissue sarcomas in adults","volume":"2","author":"Picci","year":"2000","journal-title":"Curr. Oncol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1200\/JCO.1993.11.7.1276","article-title":"An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas","volume":"11","author":"Antman","year":"1993","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1200\/JCO.2008.19.2930","article-title":"Efficacy of Sequential High-Dose Doxorubicin and Ifosfamide Compared With Standard-Dose Doxorubicin in Patients With Advanced Soft Tissue Sarcoma: An Open-Label Randomized Phase II Study of the Spanish Group for Research on Sarcomas","volume":"27","author":"Maurel","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1006\/gyno.1996.0220","article-title":"Ifosfamide and Doxorubicin in the Treatment of Advanced Leiomyosarcomas of the Uterus: A Gynecologic Oncology Group Study","volume":"62","author":"Sutton","year":"1996","journal-title":"Gynecol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1200\/JCO.2002.11.050","article-title":"Gemcitabine and Docetaxel in Patients With Unresectable Leiomyosarcoma: Results of a Phase II Trial","volume":"20","author":"Hensley","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1200\/JCO.2006.10.4117","article-title":"Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: Results of sarcoma alliance for research through collaboration study 002 [corrected]","volume":"25","author":"Maki","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1200\/JCO.2005.01.180","article-title":"Phase II Study of ET-743 in Advanced Soft Tissue Sarcomas: A European Organisation for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial","volume":"23","author":"Blay","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1200\/JCO.2008.21.0088","article-title":"Efficacy and Safety of Trabectedin in Patients With Advanced or Metastatic Liposarcoma or Leiomyosarcoma After Failure of Prior Anthracyclines and Ifosfamide: Results of a Randomized Phase II Study of Two Different Schedules","volume":"27","author":"Demetri","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1200\/JCO.2015.62.4734","article-title":"Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial","volume":"34","author":"Demetri","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1200\/JCO.2008.21.3223","article-title":"Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: A phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043)","volume":"27","author":"Sleijfer","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1016\/S0140-6736(12)60651-5","article-title":"Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"379","author":"Blay","year":"2012","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ygyno.2014.11.011","article-title":"Impact of morcellation on survival outcomes of patients with unexpected uterine leiomyosarcoma: A systematic review and meta-analysis","volume":"137","author":"Bogani","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.ejca.2008.01.019","article-title":"Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: An European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874)","volume":"44","author":"Reed","year":"2008","journal-title":"Eur. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1055\/a-1897-5124","article-title":"Sarcoma of the Uterus. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015\/074, April 2021)","volume":"82","author":"Denschlag","year":"2022","journal-title":"Geburtshilfe Frauenheilkd"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.ygyno.2016.07.110","article-title":"Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis","volume":"143","author":"Bogani","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.ygyno.2019.07.001","article-title":"Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis","volume":"154","author":"Chae","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/annonc\/mds545","article-title":"A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study): A study of the French Sarcoma Group","volume":"24","author":"Pautier","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s11912-009-0020-8","article-title":"Sarcomas of the head and neck region","volume":"11","author":"Shellenberger","year":"2009","journal-title":"Curr. Oncol. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/jso.21031","article-title":"The role of surgical margin status in retroperitoneal sarcoma","volume":"98","author":"Anaya","year":"2008","journal-title":"J. Surg. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.ejso.2006.07.002","article-title":"Outcomes in a series of 103 retroperitoneal sarcomas","volume":"32","author":"Pierie","year":"2006","journal-title":"Eur. J. Surg. Oncol. (EJSO)"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/01.sla.0000108670.31446.54","article-title":"Operative management of primary retroperitoneal sarcomas: A reappraisal of an institutional experience","volume":"239","author":"Hassan","year":"2004","journal-title":"Ann Surg"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1245\/s10434-017-6081-2","article-title":"External Beam Radiation Therapy for Resectable Soft Tissue Sarcoma: A Systematic Review and Meta-Analysis","volume":"25","author":"Albertsmeier","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/S1470-2045(20)30446-0","article-title":"Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): A multicentre, open-label, randomised, phase 3 trial","volume":"21","author":"Bonvalot","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3285","DOI":"10.1002\/cncr.30738","article-title":"Immunotherapy with Single Agent Nivolumab for Advanced Leiomyosarcoma of the Uterus: Results of a Phase 2 Study","volume":"123","author":"Barysauskas","year":"2017","journal-title":"Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/S1470-2045(17)30624-1","article-title":"Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): A multicentre, two-cohort, single-arm, open-label, phase 2 trial","volume":"18","author":"Tawbi","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/S1470-2045(22)00392-8","article-title":"Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: A single-centre phase 2 trial","volume":"23","author":"Somaiah","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S1470-2045(18)30006-8","article-title":"Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): Two open-label, non-comparative, randomised, phase 2 trials","volume":"19","author":"Mahoney","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Chen, Y., Liu, X., Liu, J., Liang, D., Zhao, M., Yu, W., and Chen, P. (2021). Nivolumab plus ipilimumab versus nivolumab in individuals with treatment-naive programmed death-ligand 1 positive metastatic soft tissue sarcomas: A multicentre retrospective study. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-07843-3"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.ejca.2021.04.034","article-title":"Immune checkpoint inhibitors in treatment of soft-tissue sarcoma: A systematic review and meta-analysis","volume":"152","author":"Saerens","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13045-020-00891-5","article-title":"PD1\/PD-L1 targeting in advanced soft-tissue sarcomas: A pooled analysis of phase II trials","volume":"13","author":"Italiano","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.21037\/atm-22-3963","article-title":"Efficacy of PD-1 inhibitors combined with pegylated liposomal doxorubicin and dacarbazine compared with liposomal doxorubicin and dacarbazine in advanced leiomyosarcoma patients: A retrospective, single-institutional cohort study","volume":"10","author":"Tan","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1001\/jamaoncol.2020.3689","article-title":"Assessment of Doxorubicin and Pembrolizumab in Patients With Advanced Anthracycline-Naive Sarcoma: A Phase 1\/2 Nonrandomized Clinical Trial","volume":"6","author":"Pollack","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.1158\/1078-0432.CCR-21-2001","article-title":"Phase II Study of Pembrolizumab in Combination with Doxorubicin in Metastatic and Unresectable Soft-Tissue Sarcoma","volume":"27","author":"Livingston","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e001561","DOI":"10.1136\/jitc-2020-001561","article-title":"Nivolumab and sunitinib combination in advanced soft tissue sarcomas: A multicenter, single-arm, phase Ib\/II trial","volume":"8","author":"Hindi","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S1470-2045(19)30153-6","article-title":"Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: A single-centre, single-arm, phase 2 trial","volume":"20","author":"Wilky","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"747650","DOI":"10.3389\/fmolb.2021.747650","article-title":"Activity of PD-1 Inhibitor Combined With Anti-Angiogenic Therapy in Advanced Sarcoma: A Single-Center Retrospective Analysis","volume":"8","author":"You","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"100701","DOI":"10.1016\/j.gore.2021.100701","article-title":"Use of pembrolizumab in MSI-high uterine leiomyosarcoma; a case report and review of the literature","volume":"35","author":"Wang","year":"2021","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.immuni.2017.02.001","article-title":"Loss of PTEN Is Associated with Resistance to Anti-PD-1 Checkpoint Blockade Therapy in Metastatic Uterine Leiomyosarcoma","volume":"46","author":"George","year":"2017","journal-title":"Immunity"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1093\/annonc\/mdw243","article-title":"Successful treatment of refractory leiomyosarcoma with the PD-1 inhibitor nivolumab","volume":"27","author":"Heine","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1158\/1078-0432.CCR-22-0240","article-title":"A Phase 1\/2 Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma","volume":"28","author":"Wagner","year":"2022","journal-title":"Clin Cancer Res"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4496","DOI":"10.1038\/s41467-021-24677-6","article-title":"Lineage-defined leiomyosarcoma subtypes emerge years before diagnosis and determine patient survival","volume":"12","author":"Anderson","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.cell.2017.10.014","article-title":"Cancer Genome Atlas Research, Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas","volume":"171","author":"Lazar","year":"2017","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/onc.2009.381","article-title":"Discovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling","volume":"29","author":"Beck","year":"2010","journal-title":"Oncogene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1158\/1078-0432.CCR-12-2970","article-title":"Genetic Profiling Identifies Two Classes of Soft-Tissue Leiomyosarcomas with Distinct Clinical Characteristics","volume":"19","author":"Italiano","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13073-017-0424-2","article-title":"Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden","volume":"9","author":"Chalmers","year":"2017","journal-title":"Genome Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Liu, W., Tong, H., Zhang, C., Zhuang, R., Guo, H., Lv, C., Yang, H., Lin, Q., Guo, X., and Wang, Z. (2020). Integrated genomic and transcriptomic analysis revealed mutation patterns of de-differentiated liposarcoma and leiomyosarcoma. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07456-2"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1126\/science.aaa1348","article-title":"Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non\u2013small cell lung cancer","volume":"348","author":"Rizvi","year":"2015","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMoa1406498","article-title":"Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma","volume":"371","author":"Snyder","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/S1470-2045(20)30445-9","article-title":"Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study","volume":"21","author":"Marabelle","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41568-022-00446-5","article-title":"Cancer proteogenomics: Current impact and future prospects","volume":"22","author":"Mani","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"700568","DOI":"10.3389\/fonc.2021.700568","article-title":"Somatic Copy Number Alterations in Human Cancers: An Analysis of Publicly Available Data From The Cancer Genome Atlas","volume":"11","author":"Harbers","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human cancers","volume":"463","author":"Beroukhim","year":"2010","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41467-017-02602-0","article-title":"Integrative genomic and transcriptomic analysis of leiomyosarcoma","volume":"9","author":"Chudasama","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ccell.2020.10.001","article-title":"The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker","volume":"39","author":"Jardim","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.ccell.2018.03.007","article-title":"Genomic and Functional Approaches to Understanding Cancer Aneuploidy","volume":"33","author":"Taylor","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"aaf8399","DOI":"10.1126\/science.aaf8399","article-title":"Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy","volume":"355","author":"Davoli","year":"2017","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1158\/1078-0432.CCR-14-3141","article-title":"Clinically Relevant Molecular Subtypes in Leiomyosarcoma","volume":"21","author":"Guo","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1158\/0008-5472.CAN-08-1443","article-title":"Strong Smooth Muscle Differentiation Is Dependent on Myocardin Gene Amplification in Most Human Retroperitoneal Leiomyosarcomas","volume":"69","author":"Coindre","year":"2009","journal-title":"Cancer Res"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1158\/1078-0432.CCR-10-2050","article-title":"Comprehensive Mapping of p53 Pathway Alterations Reveals an Apparent Role for Both SNP309 and MDM2 Amplification in Sarcomagenesis","volume":"17","author":"Ito","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.2353\/ajpath.2010.100104","article-title":"Constant p53 Pathway Inactivation in a Large Series of Soft Tissue Sarcomas with Complex Genetics","volume":"177","author":"Chibon","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nrc2715","article-title":"p53 and metabolism","volume":"9","author":"Vousden","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1093\/jmcb\/mjy070","article-title":"Tumor suppressor p53 and metabolism","volume":"11","author":"Liu","year":"2018","journal-title":"J. Mol. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/ncb2641","article-title":"and K.H. Vousden, p53 mutations in cancer","volume":"15","author":"Muller","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1158\/1078-0432.CCR-19-3959","article-title":"Genomic Landscape of Uterine Sarcomas Defined Through Prospective Clinical Sequencing","volume":"26","author":"Hensley","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41586-019-1906-8","article-title":"B cells are associated with survival and immunotherapy response in sarcoma","volume":"577","author":"Petitprez","year":"2020","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1002\/cncr.33542","article-title":"Relationships between highly recurrent tumor suppressor alterations in 489 leiomyosarcomas","volume":"127","author":"Schaefer","year":"2021","journal-title":"Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.trecan.2019.03.005","article-title":"Cell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy","volume":"5","author":"Knudsen","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41568-018-0008-5","article-title":"Non-canonical functions of the RB protein in cancer","volume":"18","author":"Dick","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1158\/1541-7786.MCR-18-0201","article-title":"Beyond the Cell Cycle: Enhancing the Immune Surveillance of Tumors Via CDK4\/6 Inhibition","volume":"16","author":"Chaikovsky","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e2025182118","DOI":"10.1073\/pnas.2025182118","article-title":"Integrated mutational landscape analysis of uterine leiomyosarcomas","volume":"118","author":"Choi","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/s41591-019-0434-2","article-title":"Immunogenic neoantigens derived from gene fusions stimulate T cell responses","volume":"25","author":"Yang","year":"2019","journal-title":"Nat. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.immuni.2018.03.004","article-title":"Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape","volume":"48","author":"Wellenstein","year":"2018","journal-title":"Immunity"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrc.2017.117","article-title":"Impact of oncogenic pathways on evasion of antitumour immune responses","volume":"18","author":"Spranger","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1158\/2159-8290.CD-17-0915","article-title":"CDK4\/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation","volume":"8","author":"Deng","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/j.athoracsur.2021.08.054","article-title":"Inhibition of Cyclin Dependent Kinase 4\/6 Overcomes Primary Resistance to Programmed Cell Death 1 Blockade in Malignant Mesothelioma","volume":"114","author":"Jang","year":"2022","journal-title":"Ann. Thorac. Surg."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1200\/PO.20.00063","article-title":"Combined CDK4\/6 and PD-1 Inhibition in Refractory SMARCA4-Deficient Small-Cell Carcinoma of the Ovary, Hypercalcemic Type","volume":"4","author":"Lee","year":"2020","journal-title":"JCO Precis Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature25015","article-title":"Cyclin D\u2013CDK4 kinase destabilizes PD-L1 via cullin 3\u2013SPOP to control cancer immune surveillance","volume":"553","author":"Zhang","year":"2018","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nri.2016.99","article-title":"Emerging roles of p53 and other tumour-suppressor genes in immune regulation","volume":"16","author":"Mandinova","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1002\/hep.27217","article-title":"Retinoblastoma protein potentiates the innate immune response in hepatocytes: Significance for hepatocellular carcinoma","volume":"60","author":"Hutcheson","year":"2014","journal-title":"Hepatology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.cell.2018.09.006","article-title":"A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade","volume":"175","author":"Shah","year":"2018","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"12234","DOI":"10.18632\/oncotarget.3498","article-title":"Multi-platform profiling of over 2000 sarcomas: Identification of biomarkers and novel therapeutic targets","volume":"6","author":"Movva","year":"2015","journal-title":"Oncotarget"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0065-230X(05)94002-5","article-title":"Activation of AKT Kinases in Cancer: Implications for Therapeutic Targeting","volume":"94","author":"Bellacosa","year":"2005","journal-title":"Adv. Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1106148","article-title":"Phosphorylation and regulation of Akt\/PKB by the rictor-mTOR complex","volume":"307","author":"Sarbassov","year":"2005","journal-title":"Science"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0092-8674(00)81780-8","article-title":"Negative Regulation of PKB\/Akt-Dependent Cell Survival by the Tumor Suppressor PTEN","volume":"95","author":"Stambolic","year":"1998","journal-title":"Cell"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cancergencyto.2005.01.011","article-title":"Loss of DNA copy number of 10q is associated with aggressive behavior of leiomyosarcomas: A comparative genomic hybridization study","volume":"161","author":"Hu","year":"2005","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1002\/cncr.28900","article-title":"Molecular analyses of 6 different types of uterine smooth muscle tumors: Emphasis in atypical leiomyoma","volume":"120","author":"Zhang","year":"2014","journal-title":"Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1172\/JCI66236","article-title":"Host immunity contributes to the anti-melanoma activity of BRAF inhibitors","volume":"123","author":"Knight","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6171","DOI":"10.1158\/0008-5472.CAN-10-0153","article-title":"Antiangiogenic Agents Can Increase Lymphocyte Infiltration into Tumor and Enhance the Effectiveness of Adoptive Immunotherapy of Cancer","volume":"70","author":"Shrimali","year":"2010","journal-title":"Cancer Res"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1158\/2159-8290.CD-15-0283","article-title":"Loss of PTEN Promotes Resistance to T Cell\u2013Mediated Immunotherapy","volume":"6","author":"Peng","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/CCO.0000000000000741","article-title":"Next-generation sequencing for the management of sarcomas with no known driver mutations","volume":"33","author":"Vyse","year":"2021","journal-title":"Curr. Opin. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41523-018-0066-6","article-title":"Migrating the SNP array-based homologous recombination deficiency measures to next generation sequencing data of breast cancer","volume":"4","author":"Sztupinszki","year":"2018","journal-title":"NPJ Breast Cancer"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1200\/PO.20.00122","article-title":"Clinical Outcome of Leiomyosarcomas With Somatic Alteration in Homologous Recombination Pathway Genes","volume":"4","author":"Rosenbaum","year":"2020","journal-title":"JCO Precis. Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.molonc.2011.07.001","article-title":"The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing up the misunderstandings","volume":"5","author":"Helleday","year":"2011","journal-title":"Mol. Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1126\/science.1203486","article-title":"Cancer Immunoediting: Integrating Immunity\u2019s Roles in Cancer Suppression and Promotion","volume":"331","author":"Schreiber","year":"2011","journal-title":"Science"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nrclinonc.2015.105","article-title":"Inflammation and cancer: Advances and new agents","volume":"12","author":"Crusz","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nrclinonc.2017.101","article-title":"The immune contexture in cancer prognosis and treatment","volume":"14","author":"Fridman","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Huang, J.-L., Chang, Y.-T., Hong, Z.-Y., and Lin, C.-S. (2022). Targeting DNA Damage Response and Immune Checkpoint for Anticancer Therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063238"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Y\u00e9lamos, J., Moreno-Lama, L., Jimeno, J., and Ali, S.O. (2020). Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies. Cancers, 12.","DOI":"10.3390\/cancers12020392"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/nm1197-1271","article-title":"Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines","volume":"3","author":"Bryan","year":"1997","journal-title":"Nat. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nrg2763","article-title":"Alternative lengthening of telomeres: Models, mechanisms and implications","volume":"11","author":"Cesare","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Lovejoy, C.A., Li, W., Reisenweber, S., Thongthip, S., Bruno, J., de Lange, T., De, S., Petrini, J.H.J., Sung, P.A., and Jasin, M. (2012). Loss of ATRX, Genome Instability, and an Altered DNA Damage Response Are Hallmarks of the Alternative Lengthening of Telomeres Pathway. PLOS Genet., 8.","DOI":"10.1371\/journal.pgen.1002772"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/sj.onc.1205058","article-title":"Alternative lengthening of telomeres in mammalian cells","volume":"21","author":"Henson","year":"2002","journal-title":"Oncogene"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"9948","DOI":"10.1128\/MCB.24.22.9948-9957.2004","article-title":"Telomeric DNA in ALT Cells Is Characterized by Free Telomeric Circles and Heterogeneous t-Loops","volume":"24","author":"Cesare","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1128\/MCB.00603-08","article-title":"Unusual Telomeric DNAs in Human Telomerase-Negative Immortalized Cells","volume":"29","author":"Nabetani","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1097\/PAS.0000000000000324","article-title":"Leiomyosarcoma With Alternative Lengthening of Telomeres Is Associated With Aggressive Histologic Features, Loss of ATRX Expression, and Poor Clinical Outcome","volume":"39","author":"Liau","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1016\/j.jpedsurg.2009.07.046","article-title":"Telomere biology in neuroblastoma: Telomere binding proteins and alternative strengthening of telomeres","volume":"44","author":"Onitake","year":"2009","journal-title":"J. Pediatr. Surg."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1126\/science.1257216","article-title":"Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors","volume":"347","author":"Flynn","year":"2015","journal-title":"Science"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1158\/0008-5472.CAN-22-0125","article-title":"Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function","volume":"82","author":"Macha","year":"2022","journal-title":"Cancer Res"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"7057","DOI":"10.1038\/s41467-021-27142-6","article-title":"Structural basis of reactivation of oncogenic p53 mutants by a small molecule: Methylene quinuclidinone (MQ)","volume":"12","author":"Degtjarik","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41419-019-1997-z","article-title":"Correction: APR-246 reactivates mutant p53 by targeting cysteines 124 and 277","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1158\/1078-0432.CCR-19-1824","article-title":"Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab","volume":"26","author":"Keung","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/s41591-022-01821-3","article-title":"Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: A phase 2 PEMBROSARC trial cohort","volume":"28","author":"Italiano","year":"2022","journal-title":"Nat. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.humpath.2014.11.001","article-title":"Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment","volume":"46","author":"Shoushtari","year":"2015","journal-title":"Hum. Pathol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e1386828","DOI":"10.1080\/2162402X.2017.1386828","article-title":"Increased infiltration of M2-macrophages, T-cells and PD-L1 expression in high grade leiomyosarcomas supports immunotherapeutic strategies","volume":"7","author":"Kostine","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Kim, J.R., Moon, Y.J., Kwon, K.S., Bae, J.S., Wagle, S., Kim, K.M., Park, H.S., Lee, H., Moon, W.S., and Chung, M.J. (2013). Tumor Infiltrating PD1-Positive Lymphocytes and the Expression of PD-L1 Predict Poor Prognosis of Soft Tissue Sarcomas. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082870"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e1278100","DOI":"10.1080\/2162402X.2016.1278100","article-title":"PDL1 expression is a poor-prognosis factor in soft-tissue sarcomas","volume":"6","author":"Bertucci","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/bjc.2017.434","article-title":"Mechanisms of resistance to immune checkpoint inhibitors","volume":"118","author":"Jenkins","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e14611","DOI":"10.1200\/JCO.2017.35.15_suppl.e14611","article-title":"Measurement of PD-1, TIM-3 and LAG-3 protein in non-small cell lung carcinomas (NSCLCs) with acquired resistance to PD-1 axis blockers","volume":"35","author":"Datar","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1038\/s41379-019-0312-y","article-title":"Expression of lymphocyte immunoregulatory biomarkers in bone and soft-tissue sarcomas","volume":"32","author":"Dancsok","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e109080","DOI":"10.1371\/journal.pone.0109080","article-title":"Lymphocyte Activation Gene 3 (LAG-3) Modulates the Ability of CD4 T-cells to Be Suppressed In Vivo","volume":"9","author":"Durham","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"5450","DOI":"10.4049\/jimmunol.172.9.5450","article-title":"Lymphocyte Activation Gene-3 (CD223) Regulates the Size of the Expanding T Cell Population Following Antigen Activation In Vivo","volume":"172","author":"Workman","year":"2004","journal-title":"J. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1158\/0008-5472.CAN-11-1620","article-title":"Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape","volume":"72","author":"Woo","year":"2012","journal-title":"Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41586-022-05368-8","article-title":"Neoadjuvant relatlimab and nivolumab in resectable melanoma","volume":"611","author":"Amaria","year":"2022","journal-title":"Nature"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"331","DOI":"10.20892\/j.issn.2095-3941.2018.0306","article-title":"LAG-3 expression on tumor-infiltrating T cells in soft tissue sarcoma correlates with poor survival","volume":"16","author":"Que","year":"2019","journal-title":"Cancer Biol. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1007\/s00432-020-03390-9","article-title":"Association of PD-L1 and IDO1 expression with JAK\u2013STAT pathway activation in soft-tissue leiomyosarcoma","volume":"147","author":"Iwasaki","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_152","unstructured":"(2022, November 15). A Study of BMS-986205 Alone and in Combination with Nivolumab in Chinese Patients with Advanced Malignant Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03792750."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1182\/blood-2017-06-741041","article-title":"Immunotherapy targeting 4-1BB: Mechanistic rationale, clinical results, and future strategies","volume":"131","author":"Chester","year":"2018","journal-title":"Blood"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/s41467-021-21383-1","article-title":"Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells","volume":"12","author":"Duhen","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2066050","DOI":"10.1080\/2162402X.2022.2066050","article-title":"OX40 and 4-1BB delineate distinct immune profiles in sarcoma","volume":"11","author":"Melake","year":"2022","journal-title":"Oncoimmunology"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1158\/0008-5472.CAN-16-0839","article-title":"Adaptive NK Cells with Low TIGIT Expression Are Inherently Resistant to Myeloid-Derived Suppressor Cells","volume":"76","author":"Sarhan","year":"2016","journal-title":"Cancer Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e000957","DOI":"10.1136\/jitc-2020-000957","article-title":"TIGIT in cancer immunotherapy","volume":"8","author":"Chauvin","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s41590-018-0132-0","article-title":"Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity","volume":"19","author":"Zhang","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"e001355","DOI":"10.1136\/jitc-2020-001355","article-title":"Analysis of tumor-infiltrating NK and T cells highlights IL-15 stimulation and TIGIT blockade as a combination immunotherapy strategy for soft tissue sarcomas","volume":"8","author":"Judge","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/path.1027","article-title":"The role of tumour-associated macrophages in tumour progression: Implications for new anticancer therapies","volume":"196","author":"Bingle","year":"2002","journal-title":"J. Pathol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nrc1256","article-title":"Tumour-educated macrophages promote tumour progression and metastasis","volume":"4","author":"Pollard","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1189\/jlb.0905495","article-title":"Monocyte\/macrophage infiltration in tumors: Modulators of angiogenesis","volume":"80","author":"Dirkx","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_163","first-page":"4281","article-title":"Clinical effects of tumor-associated macrophages and dendritic cells on renal cell carcinoma","volume":"22","author":"Hamada","year":"2002","journal-title":"Anticancer. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1046\/j.1442-2042.2000.00190.x","article-title":"Prognostic value of tumor-associated macrophage count in human bladder cancer","volume":"7","author":"Hanada","year":"2000","journal-title":"Int. J. Urol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1111\/j.1572-0241.2004.30733.x","article-title":"Significance of macrophage chemoattractant protein-1 expression and macrophage infiltration in squamous cell carcinoma of the esophagus","volume":"99","author":"Koide","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/sj.bjc.6690158","article-title":"Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast","volume":"79","author":"Leek","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1158\/1078-0432.CCR-07-1712","article-title":"Prognostic Significance of Macrophage Infiltration in Leiomyosarcomas","volume":"14","author":"Lee","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"39833","DOI":"10.1074\/jbc.M203287200","article-title":"Negative Regulation of Platelet Clearance and of the Macrophage Phagocytic Response by the Transmembrane Glycoprotein SHPS-1","volume":"277","author":"Yamao","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1747340","DOI":"10.1080\/2162402X.2020.1747340","article-title":"Tumor-associated macrophages and macrophage-related immune checkpoint expression in sarcomas","volume":"9","author":"Dancsok","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMoa1807315","article-title":"CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin\u2019s Lymphoma","volume":"379","author":"Advani","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1200\/JCO.18.02018","article-title":"First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers","volume":"37","author":"Sikic","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Ozaniak, A., Smetanova, J., Bartolini, R., Rataj, M., Capkova, L., Hacek, J., Fialova, M., Krupickova, L., Striz, I., and Lischke, R. (2022). A novel anti-CD47-targeted blockade promotes immune activation in human soft tissue sarcoma but does not potentiate anti-PD-1 blockade. J. Cancer Res. Clin. Oncol., 1\u201313.","DOI":"10.1007\/s00432-022-04292-8"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/7\/2099\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:08:04Z","timestamp":1760123284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/7\/2099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":172,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cancers15072099"],"URL":"https:\/\/doi.org\/10.3390\/cancers15072099","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]}}}