Publications
Clonally-Expanded, Thyrotoxic Autoimmune Mediator CD8+ T cells Driven by IL21 Contribute to Checkpoint Inhibitor Thyroiditis
published in Science Tanslational Medicine
Using single cell RNA sequencing of thyroid specimens from patients with checkpoint inhibitor thyroiditis, we identity clonally-expanded CD8+ autoimmune mediator T cells as a defining feature. Furthermore, we demonstrate that these thyrotoxic CD8+ T cells are driven by IL21 from T follicular and T peripheral helper T cells, a shared mechanism with Hashimoto's thyroiditis. We validated these findings in a mouse model of IRAEs and further show that inhibition of IL21 signaling protects against ICI-related autoimmunity.
Inhibition of the IL-17A axis Protects against Thyroid
Immune-related Adverse Events while Supporting Checkpoint Inhibitor Anti-tumor Efficacy
We report a novel physiologically relevant mouse model of immune checkpoint inhibitor autoimmune toxicities (IrAEs) and identify Type 3 Immunity (IL-17 producing T cell subsets) as key contributors to this disease process. By blocking the IL-17 axis, we show that autoimmune toxicties can be reduced, but anti-tumor immunity preserved.
Immune related adverse events from Checkpoint Immunotherapy
Tsai K, Ma H, Liang TZ, Xing Y, Chung S, Dorff T, Bell D, Lechner MG. The Combined Effect of Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors on Thyroid Function. Thyroid. 2024 Feb;34(2):158-166. doi: 10.1089/thy.2023.0542. Epub 2024 Jan 8. PMID: 38069567; PMCID: PMC10884548.
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Hilder R, et al. Safety of Immune Checkpoint Inhibitor Cancer Therapy in patients with Pre-existing Type 1 Diabetes Mellitus: A Multi-Center Cohort Study. Front. Endocrinol., 31 October 2023, https://doi.org/10.3389/fendo.2023.1242830
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El Zarif T, and the CATCH-IT Consortium. Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium. J Clin Oncol. 2023 May 16:JCO2202459. doi: 10.1200/JCO.22.02459. PMID: 37192435.
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Quandt Z, Kim S, Villanueva-Meyer J, Coupe C, Young A, Kang JH, Yazdany J, Schmajuk G, Rush S, Ziv E, Perdigoto AL, Herold K, Lechner MG, Su MA, Tyrrell JB, Bluestone J, Anderson M, Masharani U.J Endocr Soc. 2023 Feb 6;7(4):bvad012. 2023 Feb 9.PMID: 36860908
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Inhibition of the IL-17A axis Protects against Thyroid Immune-related Adverse Events while Supporting Checkpoint Inhibitor Anti-tumor Efficacy.
Lechner MG, Cheng MI, Patel AY, Hoang AT, Yakobian N, Astourian M, Pioso MS, Rodriguez ED, McCarthy EC, Hugo W, Angell TE, Drakaki A, Ribas A, Su MA.
J Immunology, August, 2022, ji2200244; DOI: https://doi.org/10.4049/jimmunol.2200244
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Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology.
Thompson JA, Schneider BJ, Brahmer J, Achufusi A, Armand P, Berkenstock MK, Bhatia S, Budde LE, Chokshi S, Davies M, Elshoury A, Gesthalter Y, Hegde A, Jain M, Kaffenberger BH, Lechner MG, Li T, Marr A, McGettigan S, McPherson J, Medina T, Mohindra NA, Olszanski AJ, Oluwole O, Patel SP, Patil P, Reddy S, Ryder M, Santomasso B, Shofer S, Sosman JA, Wang Y, Zaha VG, Lyons M, Dwyer M, Hang L.
J Natl Compr Canc Netw. 2022 Apr;20(4):387-405. doi: 10.6004/jnccn.2022.0020.
PMID: 35390769 Review.
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Optimal Thyroid Hormone Replacement Dose in Immune Checkpoint Inhibitor-Associated Hypothyroidism Is Distinct from Hashimoto's Thyroiditis.
Mosaferi T, Tsai K, Sovich S, Wilhalme H, Kathuria-Prakash N, Praw SS, Drakaki A, Angell TE, Lechner MG.
Thyroid. 2022 May;32(5):496-504. doi: 10.1089/thy.2021.0685. Epub 2022 Mar 31.
PMID: 35199588
Polyendocrine Autoimmunity and Diabetic Ketoacidosis Following Anti-PD-1 and Interferon α.
Dasgupta A, Tsay E, Federman N, Lechner MG, Su MA.
Pediatrics. 2022 Apr 1;149(4):e2021053363. doi: 10.1542/peds.2021-053363.
PMID: 35274131
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Insights into immune checkpoint inhibitor-induced thyroiditis.
Lechner MG, Ryder M.
Nat Rev Endocrinol. 2021 Nov;17(11):643-644. doi: 10.1038/s41574-021-00557-3.
PMID: 34471237
Autoimmune Disease
Sex Differences in Immunity.
Wilkinson NM, Chen HC, Lechner MG, Su MA.
Annu Rev Immunol. 2022 Apr 26;40:75-94. doi: 10.1146/annurev-immunol-101320-125133. Epub 2022 Jan 5.
PMID: 34985929 Review.
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Pathogenic TNF-α drives peripheral nerve inflammation in an Aire-deficient model of autoimmunity.
Wang Y, Guo L, Yin X, McCarthy EC, Cheng MI, Hoang AT, Chen HC, Patel AY, Allard Trout D, Xu E, Yakobian N, Hugo W, Howard JF Jr, Sheu KM, Hoffmann A, Lechner MG, Su MA.
Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2114406119. doi: 10.1073/pnas.2114406119.
PMID: 35058362
Myeloid-derived Suppressor Cells
Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent.
Angell TE, Lechner MG, Smith AM, Martin SE, Groshen SG, Maceri DR, Singer PA, Epstein AL.
Thyroid. 2016 Mar;26(3):381-9. doi: 10.1089/thy.2015.0289. Epub 2016 Feb 10.
PMID: 26756227
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Functional characterization of human Cd33+ and Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines.
Lechner MG, Megiel C, Russell SM, Bingham B, Arger N, Woo T, Epstein AL.
J Transl Med. 2011 Jun 9;9:90. doi: 10.1186/1479-5876-9-90.
PMID: 21658270
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A new mechanism for blocking myeloid-derived suppressor cells by CpG.
Lechner MG, Epstein AL.
Clin Cancer Res. 2011 Apr 1;17(7):1645-8. doi: 10.1158/1078-0432.CCR-11-0024. Epub 2011 Feb 2.
PMID: 21288925
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Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells.
Lechner MG, Liebertz DJ, Epstein AL.
J Immunol. 2010 Aug 15;185(4):2273-84. doi: 10.4049/jimmunol.1000901. Epub 2010 Jul 19.
PMID: 20644162
Cancer immunotherapy and immune escape
MHC class I loss is a frequent mechanism of immune escape in papillary thyroid cancer that is reversed by interferon and selumetinib treatment in vitro.
Angell TE, Lechner MG, Jang JK, LoPresti JS, Epstein AL.
Clin Cancer Res. 2014 Dec 1;20(23):6034-44. doi: 10.1158/1078-0432.CCR-14-0879. Epub 2014 Oct 7.
PMID: 25294906
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BRAF V600E in papillary thyroid carcinoma is associated with increased programmed death ligand 1 expression and suppressive immune cell infiltration.
Angell TE, Lechner MG, Jang JK, Correa AJ, LoPresti JS, Epstein AL.
Thyroid. 2014 Sep;24(9):1385-93. doi: 10.1089/thy.2014.0134. Epub 2014 Jul 15.
PMID: 24955518
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Immunogenicity of murine solid tumor models as a defining feature of in vivo behavior and response to immunotherapy.
Lechner MG, Karimi SS, Barry-Holson K, Angell TE, Murphy KA, Church CH, Ohlfest JR, Hu P, Epstein AL.
J Immunother. 2013 Nov-Dec;36(9):477-89. doi: 10.1097/01.cji.0000436722.46675.4a.
PMID: 24145359
Generation of tumor-targeted antibody-CpG conjugates.
Li Z, Jang JK, Lechner MG, Hu P, Khawli L, Scannell CA, Epstein AL.
J Immunol Methods. 2013 Mar 29;389(1-2):45-51. doi: 10.1016/j.jim.2012.12.009. Epub 2012 Dec 29.
PMID: 23279945
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Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma.
Russell S, Angell T, Lechner M, Liebertz D, Correa A, Sinha U, Kokot N, Epstein A.
Head Neck Oncol. 2013 Feb 27;5(3):24.
PMID: 24723971
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An in vivo immunotherapy screen of costimulatory molecules identifies Fc-OX40L as a potent reagent for the treatment of established murine gliomas.
Murphy KA, Lechner MG, Popescu FE, Bedi J, Decker SA, Hu P, Erickson JR, O'Sullivan MG, Swier L, Salazar AM, Olin MR, Epstein AL, Ohlfest JR.
Clin Cancer Res. 2012 Sep 1;18(17):4657-68. doi: 10.1158/1078-0432.CCR-12-0990. Epub 2012 Jul 10.
PMID: 22781551
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Chemokines, costimulatory molecules and fusion proteins for the immunotherapy of solid tumors.
Lechner MG, Russell SM, Bass RS, Epstein AL.
Immunotherapy. 2011 Nov;3(11):1317-40. doi: 10.2217/imt.11.115.
PMID: 22053884
Translational models of human cancer
Survival signals and targets for therapy in breast implant-associated ALK--anaplastic large cell lymphoma.
Lechner MG, Megiel C, Church CH, Angell TE, Russell SM, Sevell RB, Jang JK, Brody GS, Epstein AL.
Clin Cancer Res. 2012 Sep 1;18(17):4549-59. doi: 10.1158/1078-0432.CCR-12-0101. Epub 2012 Jul 12.
PMID: 22791880
Breast implant-associated, ALK-negative, T-cell, anaplastic, large-cell lymphoma: establishment and characterization of a model cell line (TLBR-1) for this newly emerging clinical entity.
Lechner MG, Lade S, Liebertz DJ, Prince HM, Brody GS, Webster HR, Epstein AL.
Cancer. 2011 Apr 1;117(7):1478-89. doi: 10.1002/cncr.25654. Epub 2010 Nov 8.
PMID: 21425149
Anaplastic large cell lymphoma occurring in women with breast implants: analysis of 173 cases.
Brody GS, Deapen D, Taylor CR, Pinter-Brown L, House-Lightner SR, Andersen JS, Carlson G, Lechner MG, Epstein AL.
Plast Reconstr Surg. 2015 Mar;135(3):695-705. doi: 10.1097/PRS.0000000000001033.
PMID: 25490535
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Establishment and characterization of a new human extragonadal germ cell line, SEM-1, and its comparison with TCam-2 and JKT-1.
Russell SM, Lechner MG, Mokashi A, Megiel C, Jang JK, Taylor CR, Looijenga LH, French CA, Epstein AL.
Urology. 2013 Feb;81(2):464.e1-9. doi: 10.1016/j.urology.2012.09.029.
PMID: 23374840
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USC-HN2, a new model cell line for recurrent oral cavity squamous cell carcinoma with immunosuppressive characteristics.
Russell SM, Lechner MG, Gong L, Megiel C, Liebertz DJ, Masood R, Correa AJ, Han J, Puri RK, Sinha UK, Epstein AL.
Oral Oncol. 2011 Sep;47(9):810-7. doi: 10.1016/j.oraloncology.2011.05.015. Epub 2011 Jun 29.
PMID: 21719345
Establishment and characterization of a novel head and neck squamous cell carcinoma cell line USC-HN1.
Liebertz DJ, Lechner MG, Masood R, Sinha UK, Han J, Puri RK, Correa AJ, Epstein AL.
Head Neck Oncol. 2010 Feb 22;2:5. doi: 10.1186/1758-3284-2-5.
PMID: 20175927
Thyroid Cancer & Clinical Thyroidology
Thyroid Nodules and Cancer in the Elderly.
Lechner MG, Hershman JM.
2022 Jan 11. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.
PMID: 25905203
Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer.
Schumm MA, Lechner MG, Shu ML, Ochoa JE, Kim J, Tseng CH, Leung AM, Yeh MW.
Endocr Pract. 2021 Jul;27(7):691-697. doi: 10.1016/j.eprac.2021.01.004. Epub 2021 Jan 15.
PMID: 33642257
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Changes in Stage Distribution and Disease-Specific Survival in Differentiated Thyroid Cancer with Transition to American Joint Committee on Cancer 8th Edition: A Systematic Review and Meta-Analysis.
Lechner MG, Bernardo AC, Lampe A, Praw SS, Tam SH, Angell TE.
Oncologist. 2021 Feb;26(2):e251-e260. doi: 10.1634/theoncologist.2020-0306.
PMID: 32864832
Treatment of Differentiated Thyroid Carcinomas.
Lechner MG, Praw SS, Angell TE.
Surg Pathol Clin. 2019 Dec;12(4):931-942. doi: 10.1016/j.path.2019.08.003. Epub 2019 Sep 27.
PMID: 31672299 Review.
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Bridging the Gap.
Lee JT, Lechner MG, Vaidya A, Weinmann M.
N Engl J Med. 2019 Jan 31;380(5):e6. doi: 10.1056/NEJMimc1716605.
PMID: 30699317
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Risk Factors for New Hypothyroidism During Tyrosine Kinase Inhibitor Therapy in Advanced Nonthyroidal Cancer Patients.
Lechner MG, Vyas CM, Hamnvik OR, Alexander EK, Larsen PR, Choueiri TK, Angell TE.
Thyroid. 2018 Apr;28(4):437-444. doi: 10.1089/thy.2017.0579.
PMID: 29652599
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Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers.
Lechner MG, Vyas CM, Hamnvik OR, Alexander EK, Larsen PR, Choueiri TK, Angell TE.
Thyroid. 2018 Apr;28(4):445-453. doi: 10.1089/thy.2017.0587.
PMID: 29652597
​Clinical features and hospital outcomes in thyroid storm: a retrospective cohort study.
Angell TE, Lechner MG, Nguyen CT, Salvato VL, Nicoloff JT, LoPresti JS.
J Clin Endocrinol Metab. 2015 Feb;100(2):451-9. doi: 10.1210/jc.2014-2850. Epub 2014 Oct 24.
PMID: 25343237
Cancer in the Time of COVID19
Factors Associated With Hospitalization Among Breast Cancer Patients With COVID-19: A Diverse Multi-Center Los Angeles Cohort Study.
Kathuria-Prakash N, Antrim L, Hornstein N, Sun AW, Kang IM, Baclig NV, Angell TE, Lechner MG, Wald-Dickler N, In GK.
Clin Breast Cancer. 2022 Jun;22(4):e558-e566. doi: 10.1016/j.clbc.2021.12.005.
PMID: 35027318
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​COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study.
Kathuria-Prakash N, Mosaferi T, Xie M, Antrim L, Angell TE, In GK, Su MA, Lechner MG.
Endocr Pract. 2021 Feb;27(2):90-94. doi: 10.1016/j.eprac.2020.12.013.
PMID: 33551317