Understanding the landscape of immunotherapy in thymic epithelial tumors.
immune checkpoint blockade
immunotherapy
thymic carcinoma
thymoma
tumor immune microenvironment
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
15 04 2023
15 04 2023
Historique:
revised:
22
12
2022
received:
08
10
2022
accepted:
03
01
2023
pubmed:
23
2
2023
medline:
25
3
2023
entrez:
22
2
2023
Statut:
ppublish
Résumé
Thymic epithelial tumors (TETs) are a rare group of malignancies arising from the thymus. Surgery remains the foundation of treatment for patients with early-stage disease. Limited treatment options are available for the treatment of unresectable, metastatic, or recurrent TETs and are associated with modest clinical efficacy. The emergence of immunotherapies in the treatment of solid tumors has generated significant interest in understanding their role in TET treatment. However, the high rates of comorbid paraneoplastic autoimmune disorders, particularly in thymoma, have tempered expectations regarding the role of immune-based therapies. Clinical studies of immune checkpoint blockade (ICB) in thymoma and thymic carcinoma have revealed higher frequencies of immune-related adverse events (IRAEs) and limited efficacy. Despite these setbacks, the growing understanding of the thymic tumor microenvironment and systemic immune system has advanced the understanding of these diseases and provided opportunities for novel immunotherapy modalities. Ongoing studies are evaluating numerous immune-based treatments in TETs with the goal of improving clinical efficacy and mitigating IRAE risk. This review will provide insight into the current understanding of the thymic immune microenvironment, outcomes of previous ICB studies, and review treatments currently being explored for the management of TET.
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1162-1172Subventions
Organisme : Indiana University Melvin and Bren Simon Comprehensive Cancer Center
ID : P30CA082709
Informations de copyright
© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
Références
Engels EA. Epidemiology of thymoma and associated malignancies. J Thorac Oncol. 2010;5(10 suppl 4):S260-S265. doi:10.1097/JTO.0b013e3181f1f62d
Hsu C-H, Chan JK, Yin C-H, Lee C-C, Chern C-U, Liao C-I. Trends in the incidence of thymoma, thymic carcinoma, and thymic neuroendocrine tumor in the United States. PLOS ONE. 2020;14(12):e0227197. doi:10.1371/journal.pone.0227197
Gaur P, Leary C, Yao JC. Thymic neuroendocrine tumors: a SEER database analysis of 160 patients. Ann Surg. 2010;251(6):1117-1121. doi:10.1097/SLA.0b013e3181dd4ec4
Chan JK, Rosai J. Tumors of the neck showing thymic or related branchial pouch differentiation: a unifying concept. Hum Pathol. 1991;22(4):349-367. doi:10.1016/0046-8177(91)90083-2
Pescarmona E, Rendina EA, Venuta F, Ricci C, Ruco LP, Baroni CD. The prognostic implication of thymoma histologic subtyping. A study of 80 consecutive cases. Am J Clin Pathol. 1990;93(2):190-195. doi:10.1093/ajcp/93.2.190
Maggi G, Casadio C, Cavallo A, Cianci R, Molinatti M, Ruffini E. Thymoma: results of 241 operated cases. Ann Thorac Surg. 1991;51(1):152-156. doi:10.1016/0003-4975(91)90478-9
Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer. 1981;48(11):2485-2492. doi:10.1002/1097-0142(19811201)48:11<2485::aid-cncr2820481123>3.0.co;2-r
Koga K, Matsuno Y, Noguchi M, et al. A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int. 1994;44(5):359-367. doi:10.1111/j.1440-1827.1994.tb02936.x
Marx A, Chan JKC, Chalabreysse L, et al. The 2021 WHO Classification of Tumors of the Thymus and Mediastinum: what is new in thymic epithelial, germ cell, and mesenchymal tumors? J Thorac Oncol. 2022;17(2):200-213. doi:10.1016/j.jtho.2021.10.010
Lamarca A, Moreno V, Feliu J. Thymoma and thymic carcinoma in the target therapies era. Cancer Treat Rev. 2013;39(5):413-420. doi:10.1016/j.ctrv.2012.11.005
Conforti F, Pala L, Giaccone G, De Pas T. Thymic epithelial tumors: from biology to treatment. Cancer Treat Rev. 2020;86:102014. doi:10.1016/j.ctrv.2020.102014
Jung HA, Kim M, Kim HS, et al. A phase 2 study of palbociclib for recurrent or refractory advanced thymic epithelial tumors (KCSG LU17-21). J Thorac Oncol. 2022;18:223-231. doi:10.1016/j.jtho.2022.10.008
Lippner EA, Lewis DB, Robinson WH, Katsumoto TR. Paraneoplastic and therapy-related immune complications in thymic malignancies. Curr Treat Options Oncol. 2019;20(7):62. doi:10.1007/s11864-019-0661-2
Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Strobel P. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev. 2013;12(9):875-884. doi:10.1016/j.autrev.2013.03.007
Weksler B, Lu B. Alterations of the immune system in thymic malignancies. J Thorac Oncol. 2014;9(suppl 2):S137-S142. doi:10.1097/JTO.0000000000000299
Bernard C, Frih H, Pasquet F, et al. Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev. 2016;15(1):82-92. doi:10.1016/j.autrev.2015.09.005
Padda SK, Yao X, Antonicelli A, et al. Paraneoplastic syndromes and thymic malignancies: an examination of the International Thymic Malignancy Interest Group retrospective database. J Thorac Oncol. 2018;13(3):436-446. doi:10.1016/j.jtho.2017.11.118
Carter BW, Okumura M, Detterbeck FC, Marom EM. Approaching the patient with an anterior mediastinal mass: a guide for radiologists. J Thorac Oncol. 2014;9(9 Suppl 2):S110-S118. doi:10.1097/JTO.0000000000000295
Marx A, Chan JK, Coindre JM, et al. The 2015 World Health Organization Classification of Tumors of the Thymus: continuity and changes. J Thorac Oncol. 2015;10(10):1383-1395. doi:10.1097/JTO.0000000000000654
Masaoutis C, Palamaris K, Kokkali S, Levidou G, Theocharis S. Unraveling the immune microenvironment of thymic epithelial tumors: implications for autoimmunity and treatment. Int J Mol Sci. 2022;16(14):23. doi:10.3390/ijms23147864
Chen Y, Zhang XS, Wang YG, Lu C, Li J, Zhang P. Imbalance of Th17 and Tregs in thymoma may be a pathological mechanism of myasthenia gravis. Mol Immunol. 2021;133:67-76. doi:10.1016/j.molimm.2021.02.011
Hoffacker V, Schultz A, Tiesinga JJ, et al. Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood. 2000;96(12):3872-3879. doi:10.1182/blood.v96.12.3872.h8003872_3872_3879
Xin Z, Lin M, Hao Z, et al. The immune landscape of human thymic epithelial tumors. Nat Commun. 2022;13(1):5463. doi:10.1038/s41467-022-33170-7
Omatsu M, Kunimura T, Mikogami T, et al. Difference in distribution profiles between CD163+ tumor-associated macrophages and S100+ dendritic cells in thymic epithelial tumors. Diagn Pathol. 2014;9(1):215. doi:10.1186/s13000-014-0215-7
Sato J, Kitano S, Motoi N, et al. CD20(+) tumor-infiltrating immune cells and CD204(+) M2 macrophages are associated with prognosis in thymic carcinoma. Cancer Sci. 2020;111(6):1921-1932. doi:10.1111/cas.14409
Yuan X, Huang L, Luo W, et al. Diagnostic and prognostic significances of SOX9 in thymic epithelial tumor. Front Oncol. 2021;11:708735. doi:10.3389/fonc.2021.708735
Sato J, Fujiwara M, Kawakami T, et al. Fascin expression in dendritic cells and tumor epithelium in thymoma and thymic carcinoma. Oncol Lett. 2011;2(6):1025-1032. doi:10.3892/ol.2011.383
Katsuya Y, Fujita Y, Horinouchi H, Ohe Y, Watanabe S, Tsuta K. Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma. Lung Cancer. 2015;88(2):154-159. doi:10.1016/j.lungcan.2015.03.003
Yokoyama S, Miyoshi H, Nakashima K, et al. Prognostic value of programmed death ligand 1 and programmed death 1 expression in thymic carcinoma. Clin Cancer Res. 2016;22(18):4727-4734. doi:10.1158/1078-0432.CCR-16-0434
Rajan A, Heery CR, Thomas A, et al. Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma. J Immunother Cancer. 2019;7(1):269. doi:10.1186/s40425-019-0723-9
Rouquette I, Taranchon-Clermont E, Gilhodes J, et al. Immune biomarkers in thymic epithelial tumors: expression patterns, prognostic value and comparison of diagnostic tests for PD-L1. Biomark Res. 2019;7(1):28. doi:10.1186/s40364-019-0177-8
Arbour KC, Naidoo J, Steele KE, et al. Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors. PLoS One. 2017;12(8):e0182665. doi:10.1371/journal.pone.0182665
Marcus L, Fashoyin-Aje LA, Donoghue M, et al. FDA Approval summary: pembrolizumab for the treatment of tumor mutational burden-high solid tumors. Clin Cancer Res. 2021;27(17):4685-4689. doi:10.1158/1078-0432.CCR-21-0327
Radovich M, Pickering CR, Felau I, et al. The integrated genomic landscape of thymic epithelial tumors. Cancer Cell. 2018;33(2):244-258. e10. doi:10.1016/j.ccell.2018.01.003
Girard N, Basse C, Schrock A, Ramkissoon S, Killian K, Ross JS. Comprehensive genomic profiling of 274 thymic epithelial tumors unveils oncogenic pathways and predictive biomarkers. Oncologist. 2022;27(11):919-929. doi:10.1093/oncolo/oyac115
Repetto M, Conforti F, Pirola S, et al. Thymic carcinoma with Lynch syndrome or microsatellite instability, a rare entity responsive to immunotherapy. Eur J Cancer. 2021;153:162-167. doi:10.1016/j.ejca.2021.05.029
Kurokawa K, Shukuya T, Greenstein R, et al. Genomic characterization of thymic epithelial tumor from real-world data. J Clin Oncol. 2022;40(16_Suppl l):8587. doi:10.1200/JCO.2022.40.16_suppl.8587
Benitez AA, Khalil-Aguero S, Nandakumar A, et al. Absence of central tolerance in Aire-deficient mice synergizes with immune-checkpoint inhibition to enhance antitumor responses. Commun Biol. 2020;3(1):355. doi:10.1038/s42003-020-1083-1
Saxena M, van der Burg SH, Melief CJM, Bhardwaj N. Therapeutic cancer vaccines. Nat Rev Cancer. 2021;21(6):360-378. doi:10.1038/s41568-021-00346-0
Gout DY, Groen LS, van Egmond M. The present and future of immunocytokines for cancer treatment. Cell Mol Life Sci. 2022;79(10):509. doi:10.1007/s00018-022-04514-9
Zheng X, Wu Y, Bi J, et al. The use of supercytokines, immunocytokines, engager cytokines, and other synthetic cytokines in immunotherapy. Cell Mol Immunol. 2022;19(2):192-209. doi:10.1038/s41423-021-00786-6
Gbolahan OB, Porter RF, Salter JT, et al. A phase ii study of pemetrexed in patients with recurrent thymoma and thymic carcinoma. J Thorac Oncol. 2018;13(12):1940-1948. doi:10.1016/j.jtho.2018.07.094
Highley MS, Underhill CR, Parnis FX, et al. Treatment of invasive thymoma with single-agent ifosfamide. J Clin Oncol. 1999;17(9):2737-2744. doi:10.1200/jco.1999.17.9.2737
Palmieri G, Buonerba C, Ottaviano M, et al. Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a phase II trial. Future Oncol. 2014;10(14):2141-2147. doi:10.2217/fon.14.144
Thomas A, Rajan A, Berman A, et al. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol. 2015;16(2):177-186. doi:10.1016/s1470-2045(14)71181-7
Zucali PA, De Pas T, Palmieri G, et al. Phase II study of everolimus in patients with thymoma and thymic carcinoma previously treated with cisplatin-based chemotherapy. J Clin Oncol. 2018;36(4):342-349. doi:10.1200/JCO.2017.74.4078
Sato J, Satouchi M, Itoh S, et al. Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial. Lancet Oncol. 2020;21(6):843-850. doi:10.1016/s1470-2045(20)30162-5
Giaccone G, Kim C, Thompson J, et al. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol. 2018;19(3):347-355. doi:10.1016/S1470-2045(18)30062-7
Giaccone G, Kim C. Durable response in patients with thymic carcinoma treated with pembrolizumab after prolonged follow-up. J Thorac Oncol. 2021;16(3):483-485. doi:10.1016/j.jtho.2020.11.003
Cho J, Kim HS, Ku BM, et al. Pembrolizumab for patients with refractory or relapsed thymic epithelial tumor: an open-label phase II trial. J Clin Oncol. 2019;37(24):2162-2170. doi:10.1200/JCO.2017.77.3184
Katsuya Y, Horinouchi H, Seto T, et al. Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study. Eur J Cancer. 2019;113:78-86. doi:10.1016/j.ejca.2019.03.012
Conforti F, Zucali PA, Pala L, et al. Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(10):1287-1296. doi:10.1016/s1470-2045(22)00542-3
Chen F, Zou Z, Du J, et al. Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors. J Clin Invest. 2019;129(5):2056-2070. doi:10.1172/JCI99538
Oji Y, Inoue M, Takeda Y, et al. WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies. Int J Cancer. 2018;142(11):2375-2382. doi:10.1002/ijc.31253
Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833. doi:10.1056/NEJMoa1606774
Wolchok JD, Rollin L, Larkin J. Nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(25):2503-2504. doi:10.1056/NEJMc1714339
Mammen AL, Rajan A, Pak K, et al. Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia are associated with the development of myositis in patients with thymoma treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1. Ann Rheum Dis. 2019;78(1):150-152. doi:10.1136/annrheumdis-2018-213777
He Y, Ramesh A, Gusev Y, Bhuvaneshwar K, Giaccone G. Molecular predictors of response to pembrolizumab in thymic carcinoma. Cell Rep Med. 2021;2(9):100392. doi:10.1016/j.xcrm.2021.100392
Harbour JW, Onken MD, Roberson ED, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330(6009):1410-1413. doi:10.1126/science.1194472
Figueiredo CR, Kalirai H, Sacco JJ, et al. Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development. J Pathol. 2020;250(4):420-439. doi:10.1002/path.5384
Zhu S, Zhang T, Zheng L, et al. Combination strategies to maximize the benefits of cancer immunotherapy. J Hematol Oncol. 2021;14(1):156. doi:10.1186/s13045-021-01164-5
European Organisation for Research and Treatment of Cancer. Nivolumab in patients with type B3 thymoma and thymic carcinoma (NIVOTHYM); 2023. NCT03134118. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT0313418
Beatty GL, O'Dwyer PJ, Clark J, et al. First-in-human phase I study of the oral inhibitor of indoleamine 2,3-dioxygenase-1 epacadostat (INCB024360) in patients with advanced solid malignancies. Clin Cancer Res. 2017;23(13):3269-3276. doi:10.1158/1078-0432.CCR-16-2272
Uyttenhove C, Pilotte L, Théate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9(10):1269-1274. doi:10.1038/nm934
Wei YF, Chu CY, Chang CC, et al. Different pattern of PD-L1, IDO, and FOXP3 Tregs expression with survival in thymoma and thymic carcinoma. Lung Cancer. 2018;125:35-42. doi:10.1016/j.lungcan.2018.09.002
Georgetown University. Pembrolizumab and epacadostat in patients with thymic carcinoma; 2019. NCT 02364076. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT02364076
Long GV, Dummer R, Hamid O, et al. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 2019;20(8):1083-1097. doi:10.1016/S1470-2045(19)30274-8
Gide TN, Allanson BM, Menzies AM, et al. Inter- and intrapatient heterogeneity of indoleamine 2,3-dioxygenase expression in primary and metastatic melanoma cells and the tumour microenvironment. Histopathology. 2019;74(6):817-828. doi:10.1111/his.13814
Xing B. 938P KN046 (an anti-PD-L1/CTLA-4 bispecific antibody) in combination with lenvatinib in the treatment for advanced unresectable or metastatic hepatocellular carcinoma (HCC): preliminary efficacy and safety results of a prospective phase II trial. Ann Oncol. 2021;32:S822. doi:10.1016/j.annonc.2021.08.158
Yang Y, Fang W, Huang Y, et al. A phase 2, open-label, multicenter study to evaluate the efficacy, safety, and tolerability of KN046 in combination with chemotherapy in subjects with advanced non-small cell lung cancer. J Clin Oncol. 2021;39(suppl 10):9060. doi:10.1200/JCO.2021.39.15_suppl.9060
Weill Medical College of Cornell University. A study of KN046 in patients with thymic carcinoma who failed immune checkpoint inhibitors; 2022. NCT04925947. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT04925947
Xencor I, plc I. A study of XmAb20717 in subjects with selected advanced solid tumors; 2022. NCT03517488. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT03517488
Li MO, Flavell RA. TGF-β: a master of all T cell trades. Cell. 2008;134(3):392-404. doi:10.1016/j.cell.2008.07.025
Duan J, Liu X, Chen H, et al. Impact of PD-L1, transforming growth factor-β expression and tumor-infiltrating CD8+ T cells on clinical outcome of patients with advanced thymic epithelial tumors. Thoracic Cancer. 2018;9(11):1341-1353. doi:10.1111/1759-7714.12826
National Cancer Institutes of Health Clinical C. Bintrafusp Alfa (M7824) in Subjects With Thymoma and Thymic Carcinoma; 2022. NCT04417660. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/record/NCT04417660
Yamazaki T, Buque A, Ames TD, Galluzzi L. PT-112 induces immunogenic cell death and synergizes with immune checkpoint blockers in mouse tumor models. Oncoimmunology. 2020;9(1):1721810. doi:10.1080/2162402X.2020.1721810
Bryce AH, Dronca RS, Costello BA, et al. PT-112 in advanced metastatic castrate-resistant prostate cancer (mCRPC), as monotherapy or in combination with PD-L1 inhibitor avelumab: findings from two phase I studies. J Clin Oncol. 2020;38(suppl 6):83. doi:10.1200/JCO.2020.38.6_suppl.83
National Cancer I, National Institutes of Health Clinical C. PT-112 in subjects with thymoma and thymic carcinoma; 2022. NCT05104736. Accesed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT05104736
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57-70. doi:10.1016/s0092-8674(00)81683-9
Janik S, Bekos C, Hacker P, et al. Follistatin impacts tumor angiogenesis and outcome in thymic epithelial tumors. Sci Rep. 2019;9(1):17359. doi:10.1038/s41598-019-53671-8
Stockmann C, Schadendorf D, Klose R, Helfrich I. The impact of the immune system on tumor: angiogenesis and vascular remodeling. Front Oncol. 2014;4:69. doi:10.3389/fonc.2014.00069
Lee WS, Yang H, Chon HJ, Kim C. Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity. Exp Mol Med. 2020;52(9):1475-1485. doi:10.1038/s12276-020-00500-y
Remon J, Girard N, Novello S, et al. PECATI: a multicentric, open-label, single-arm phase II study to evaluate the efficacy and safety of pembrolizumab and lenvatinib in pretreated B3-thymoma and thymic carcinoma patients. Clin Lung Cancer. 2022;23(3):e243-e246. doi:10.1016/j.cllc.2021.07.008
Dwight O, National Cancer I, Ohio State University Comprehensive Cancer C. Pembrolizumab and sunitinib malate in treating participants with refractory metastatic or unresectable thymic cancer; 2022. NCT03463460. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT03463460
Beckermann K, Bestvina CM, Whisenant JG, et al. Phase I/II study of vorolanib plus nivolumab in patients with thoracic malignancies: immunotherapy (IO) correlatives to differentiate responders from nonresponders. J Clin Oncol. 2020;38(suppl 15):e21019. doi:10.1200/JCO.2020.38.15_suppl.e21019
Lv J, Li P. Mesothelin as a biomarker for targeted therapy. Biomark Res. 2019;7(1):18. doi:10.1186/s40364-019-0169-8
Thomas A, Chen Y, Berman A, et al. Expression of mesothelin in thymic carcinoma and its potential therapeutic significance. Lung Cancer. 2016;101:104-110. doi:10.1016/j.lungcan.2016.09.015
Pan CC, Chen PC, Chou TY, Chiang H. Expression of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma. Hum Pathol. 2003;34(11):1155-1162. doi:10.1053/j.humpath.2003.07.002
Adjei AA, Bekaii-Saab TS, Berlin J, et al. Phase 1b multi-indication study of the antibody drug conjugate anetumab ravtansine in patients with mesothelin-expressing advanced or recurrent malignancies. J Clin Oncol. 2018;36(15_Suppl l):TPS2607. doi:10.1200/JCO.2018.36.15_suppl.TPS2607
Sakane T, Murase T, Okuda K, Masaki A, Nakanishi R, Inagaki H. Expression of cancer testis antigens in thymic epithelial tumors. Pathol Int. 2021;71(7):471-479. doi:10.1111/pin.13103
Forde PM, Spicer J, Girard N. Neoadjuvant nivolumab plus chemotherapy in lung cancer. Reply. N Engl J Med. 2022;387(6):572-573. doi:10.1056/NEJMc2208133
Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385(8):683-694. doi:10.1056/NEJMoa2106391
Samsung Medical C. neoadjuvant_thymic Epithelial Tumor; 2022. NCT03858582. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT03858582
Shanghai Pulmonary Hospital SC. Clinical Study of Neoadjuvant PD-1 Antibody (Toripalimab) Plus Chemotherapy for Locally Advanced Thymic Epithelial Tumor; 2022. NCT04667793. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT04667793
Alexakou Z, Liatsos G, Vasileiou N, Vamvakaris I, Mani I, Alexopoulou A. Thymic carcinoma with multiple paraneoplastic disorders. Am J Med Sci. 2021;362(3):324-330. doi:10.1016/j.amjms.2021.04.012
AG SB, a.s S, Biotech S. Study of SO-C101 and SO-C101 in combination with pembro in adult patients with advanced/metastatic solid tumors; 2022. NCT04234113. Accessed October 01, 2022. https://clinicaltrials.gov/ct2/show/NCT04234113