Melissa Lechner*

/in /by

Melissa Lechner, Ph.D.

Office Address:
CHS 57-145

Affiliations

Assistant Clinical Professor, Medicine-Endocrinology
Research Interests

Our work focuses on the balance of immune activation and immune tolerance. We study how autoimmunity arises from loss of tolerance or inhibition of natural regulatory pathways or checkpoints. On the other side, we try to leverage immune responses and reverse tolerance to improve anti-tumor immunity. As a physician scientist, my research seeks to address the most pressing clinical questions and evolves with the needs of our patients. Here are some of our current projects.

Immune checkpoint inhibitor associated autoimmunity – Immune related adverse events (IrAEs)

Checkpoint inhibitors, including anti-programmed death protein (PD-1) or ligand (PD-L1) and anti-cytotoxic T lymphocyte antigen (CTLA-4), have revolutionized oncology by producing dramatic shrinkage in many advanced tumor types. However, their benefits are limited by the development of unwanted autoimmune side effects (IrAEs) in up to 60% of patients. IrAEs can lead to hospitalizations, permanent organ damage, treatment interruption and even premature death. The cause of IrAEs remains poorly understood.

To study the mechanisms of IrAEs we developed a novel mouse model that recapitulates the multi-organ autoimmunity seen with immune checkpoint inhibitor treatment in patients. Using this model we can study development of IrAEs in both tumor-free and tumor-bearing mice. This is relevant to patients who may be treated with checkpoint inhibitors in the neoadjuvant or adjuvant settings.

Thyroid autoimmunity

Thyroid autoimmunity affects approximately 10% of women, with a strong sex bias and familial risk. Hashimoto’s thyroiditis and Graves’ disease are frequent causes of thyroid gland dysfunction. Using single cell sequencing of human thyroid specimens and a mouse model of spontaneous autoimmunity, we are studying the cause of thyroid autoimmunity to identify therapeutic targets.

New approaches to thyroid cancer treatment

While most thyroid cancer is treated with surgery and radioactive iodine (RAI), and has a good prognosis, some patients have recurrent or metastatic disease affecting the neck, lungs, and bone. Few treatment options exist for RAI-refractory metastatic thyroid cancers, but advances in genetic and tumor immunology may identify new therapeutic targets.

We showed that thyroid cancers frequently lose antigen expression as a mechanism of tumor immune escape. In addition, BRAFV600E mutated tumors have increased expression of checkpoint protein PD-L1 and immune regulatory cells (Treg, MDSC). Our group is coming clinical and translational studies to advance care for thyroid cancer patients.

Publications

A selected list of publications:

Inhibition of IL-17A Protects against Thyroid Immune-Related Adverse Events while Preserving Checkpoint Inhibitor Antitumor Efficacy. J Immunol. 2022 08 15; 209(4):696-709. 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. PMID: 35817515; PMCID: PMC9378719.

Polyendocrine Autoimmunity and Diabetic Ketoacidosis Following Anti-PD-1 and Interferon α. Pediatrics. 2022 04 01; 149(4). Dasgupta A, Tsay E, Federman N, Lechner MG, Su MA. PMID: 35274131.

Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 04; 20(4):387-405. 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. PMID: 35390769.

Optimal Thyroid Hormone Replacement Dose in Immune Checkpoint Inhibitor-Associated Hypothyroidism Is Distinct from Hashimoto’s Thyroiditis. Thyroid. 2022 05; 32(5):496-504. Mosaferi T, Tsai K, Sovich S, Wilhalme H, Kathuria-Prakash N, Praw SS, Drakaki A, Angell TE, Lechner MG. PMID: 35199588; PMCID: PMC9145255.

Pathogenic TNF-α drives peripheral nerve inflammation in an Aire-deficient model of autoimmunity. Proc Natl Acad Sci U S A. 2022 01 25; 119(4). 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, Sheu KM, Hoffmann A, Lechner MG, Su MA. PMID: 35058362; PMCID: PMC8795502.

Sex Differences in Immunity. Annu Rev Immunol. 2022 04 26; 40:75-94. Wilkinson NM, Chen HC, Lechner MG, Su MA. PMID: 34985929.

Factors Associated With Hospitalization Among Breast Cancer Patients With COVID-19: A Diverse Multi-Center Los Angeles Cohort Study. Clin Breast Cancer. 2022 06; 22(4):e558-e566. Kathuria-Prakash N, Antrim L, Hornstein N, Sun AW, Kang IM, Baclig NV, Angell TE, Lechner MG, Wald-Dickler N, In GK. PMID: 35027318; PMCID: PMC8677421.

Insights into immune checkpoint inhibitor-induced thyroiditis. Nat Rev Endocrinol. 2021 11; 17(11):643-644. Lechner MG, Ryder M. PMID: 34471237.

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer. Endocr Pract. 2021 Jul; 27(7):691-697. Schumm MA, Lechner MG, Shu ML, Ochoa JE, Kim J, Tseng CH, Leung AM, Yeh MW. PMID: 33642257.

COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study. Endocr Pract. 2021 Feb; 27(2):90-94. Kathuria-Prakash N, Mosaferi T, Xie M, Antrim L, Angell TE, In GK, Su MA, Lechner MG. PMID: 33551317; PMCID: PMC7831810.

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. Oncologist. 2021 02; 26(2):e251-e260. Lechner MG, Bernardo AC, Lampe A, Praw SS, Tam SH, Angell TE. PMID: 32864832; PMCID: PMC7873343.

Identification of Racial Inequities in Access to Specialized Inpatient Heart Failure Care at an Academic Medical Center. Circ Heart Fail. 2019 11; 12(11):e006214. Eberly LA, Richterman A, Beckett AG, Wispelwey B, Marsh RH, Cleveland Manchanda EC, Chang CY, Glynn RJ, Brooks KC, Boxer R, Kakoza R, Goldsmith J, Loscalzo J, Morse M, Lewis EF, Abel S, Adams A, Anaya J, Andrews EH, Atkinson B, Avutu V, Bachorik A, Badri O, Bailey M, Baird K, Bakshi S, Balaban D, Barshop K, Baumrin E, Bayomy O, Beamesderfer J, Becker N, Berg DD, Berman AN, Blum SM, Boardman AP, Boden K, Bonacci RA, Brown S, Campbell K, Case S, Cetrone E, Charrow A, Chiang D, Clark D, Cohen AJ, Cooper A, Cordova T, Cuneo CN, de Feria AA, Deffenbacher K, DeFilippis EM, DeGregorio G, Deutsch AJ, Diephuis B, Divakaran S, Dorschner P, Downing N, Drescher C, D’Silva KM, Dunbar P, Duong D, Earp S, Eckhardt C, Elman SA, England R, Everett K, Fedotova N, Feingold-Link T, Ferreira M, Fisher H, Foo P, Foote M, Franco I, Gilliland T, Greb J, Greco K, Grewal S, Grin B, Growdon ME, Guercio B, Hahn CK, Hasselfeld B, Haydu EJ, Hermes Z, Hildick-Smith G, Holcomb Z, Holroyd K, Horton L, Huang G, Jablonski S, Jacobs D, Jain N, Japa S, Joseph R, Kalashnikova M, Kalwani N, Kang D, Karan A, Katz JT, Kellner D, Kidia K, Kim JH, Knowles SM, Kolbe L, Kore I, Koullias Y, Kuye I, Lang J, Lawlor M, Lechner MG, Lee K, Lee S, Lee Z, Limaye N, Lin-Beckford S, Lipsyc M, Little J, Loewenthal J, Logaraj R, Lopez DM, Loriaux D, Lu Y, Ma K, Marukian N, Matias W, Mayers JR, McConnell I, McLaughlin M, Meade C, Meador C, Mehta A, Messenger E, Michaelidis C, Mirsky J, Mitten E, Mueller A, Mullur J, Munir A, Murphy E, Nagami E, Natarajan A, Nsahlai M, Nze C, Okwara N, Olds P, Paez R, Pardo M, Patel S, Petersen A, Phelan L, Pimenta E, Pipilas D, Plovanich M, Pong D, Powers BW, Rao A, Ramirez Batlle H, Ramsis M, Reichardt A, Reiger S, Rengarajan M, Rico S, Rome BN, Rosales R, Rotenstein L, Roy A, Royston S, Rozansky H, Rudder M, Ryan CE, Salgado S, Sanchez P, Schulte J, Sekar A, Semenkovich N, Shannon E, Shaw N, Shorten AB, Shrauner W, Sinnenberg L, Smithy JW, Snyder G, Sreekrishnan A, Stabenau H, Stavrou E, Stergachis A, Stern R, Stone A, Tabrizi S, Tanyos S, Thomas C, Thun H, Torres-Lockhart K, Tran A, Treasure C, Tsai FD, Tsaur S, Tschirhart E, Tuwatananurak J, Venkateswaran RV, Vishnevetsky A, Wahl L, Wall A, Wallace F, Walsh E, Wang P, Ward HB, Warner LN, Weeks LD, Weiskopf K, Wengrod J, Williams JN, Winkler M, Wong JL, Worster D, Wright A, Wunsch C, Wynter JS, Yarbrough C, Yau WY, Yazdi D, Yeh J, Yialamas MA, Yozamp N, Zambrotta M, Zon R. PMID: 31658831; PMCID: PMC7183732.

Treatment of Differentiated Thyroid Carcinomas. Surg Pathol Clin. 2019 Dec; 12(4):931-942. Lechner MG, Praw SS, Angell TE. PMID: 31672299.

Bridging the Gap. N Engl J Med. 2019 Jan 31; 380(5):e6. Lee JT, Lechner MG, Vaidya A, Weinmann M. PMID: 30699317.

Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers. Thyroid. 2018 04; 28(4):445-453. Lechner MG, Vyas CM, Hamnvik OR, Alexander EK, Larsen PR, Choueiri TK, Angell TE. PMID: 29652597.

Risk Factors for New Hypothyroidism During Tyrosine Kinase Inhibitor Therapy in Advanced Nonthyroidal Cancer Patients. Thyroid. 2018 04; 28(4):437-444. Lechner MG, Vyas CM, Hamnvik OR, Alexander EK, Larsen PR, Choueiri TK, Angell TE. PMID: 29652599.

Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent. Thyroid. 2016 Mar; 26(3):381-9. Angell TE, Lechner MG, Smith AM, Martin SE, Groshen SG, Maceri DR, Singer PA, Epstein AL. PMID: 26756227; PMCID: PMC4790214.

Anaplastic large cell lymphoma occurring in women with breast implants: analysis of 173 cases. Plast Reconstr Surg. 2015 Mar; 135(3):695-705. Brody GS, Deapen D, Taylor CR, Pinter-Brown L, House-Lightner SR, Andersen JS, Carlson G, Lechner MG, Epstein AL. PMID: 25490535.

Clinical features and hospital outcomes in thyroid storm: a retrospective cohort study. J Clin Endocrinol Metab. 2015 Feb; 100(2):451-9. Angell TE, Lechner MG, Nguyen CT, Salvato VL, Nicoloff JT, LoPresti JS. PMID: 25343237.

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. Clin Cancer Res. 2014 Dec 01; 20(23):6034-44. Angell TE, Lechner MG, Jang JK, LoPresti JS, Epstein AL. PMID: 25294906; PMCID: PMC4252612.

Adenosine A1 receptor antagonist, L-97-1, improves survival and protects the kidney in a rat model of cecal ligation and puncture induced sepsis. Eur J Pharmacol. 2014 Oct 05; 740:346-52. Wilson CN, Vance CO, Lechner MG, Matuschak GM, Lechner AJ. PMID: 25041842; PMCID: PMC4147868.

BRAF V600E in papillary thyroid carcinoma is associated with increased programmed death ligand 1 expression and suppressive immune cell infiltration. Thyroid. 2014 Sep; 24(9):1385-93. Angell TE, Lechner MG, Jang JK, Correa AJ, LoPresti JS, Epstein AL. PMID: 24955518; PMCID: PMC4148060.

Immunogenicity of murine solid tumor models as a defining feature of in vivo behavior and response to immunotherapy. J Immunother. 2013 Nov-Dec; 36(9):477-89. Lechner MG, Karimi SS, Barry-Holson K, Angell TE, Murphy KA, Church CH, Ohlfest JR, Hu P, Epstein AL. PMID: 24145359; PMCID: PMC3910494.

Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma. Head Neck Oncol. 2013 Feb 27; 5(3):24. Russell S, Angell T, Lechner M, Liebertz D, Correa A, Sinha U, Kokot N, Epstein A. PMID: 24723971; PMCID: PMC3979926.

Establishment and characterization of a new human extragonadal germ cell line, SEM-1, and its comparison with TCam-2 and JKT-1. Urology. 2013 Feb; 81(2):464.e1-9. Russell SM, Lechner MG, Mokashi A, Megiel C, Jang JK, Taylor CR, Looijenga LH, French CA, Epstein AL. PMID: 23374840; PMCID: PMC4179199.

Generation of tumor-targeted antibody-CpG conjugates. J Immunol Methods. 2013 Mar 29; 389(1-2):45-51. Li Z, Jang JK, Lechner MG, Hu P, Khawli L, Scannell CA, Epstein AL. PMID: 23279945.

Survival signals and targets for therapy in breast implant-associated ALK–anaplastic large cell lymphoma. Clin Cancer Res. 2012 Sep 01; 18(17):4549-59. Lechner MG, Megiel C, Church CH, Angell TE, Russell SM, Sevell RB, Jang JK, Brody GS, Epstein AL. PMID: 22791880.

An in vivo immunotherapy screen of costimulatory molecules identifies Fc-OX40L as a potent reagent for the treatment of established murine gliomas. Clin Cancer Res. 2012 Sep 01; 18(17):4657-68. 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. PMID: 22781551; PMCID: PMC3432688.

Chemokines, costimulatory molecules and fusion proteins for the immunotherapy of solid tumors. Immunotherapy. 2011 Nov; 3(11):1317-40. Lechner MG, Russell SM, Bass RS, Epstein AL. PMID: 22053884; PMCID: PMC3226699.

USC-HN2, a new model cell line for recurrent oral cavity squamous cell carcinoma with immunosuppressive characteristics. Oral Oncol. 2011 Sep; 47(9):810-7. Russell SM, Lechner MG, Gong L, Megiel C, Liebertz DJ, Masood R, Correa AJ, Han J, Puri RK, Sinha UK, Epstein AL. PMID: 21719345; PMCID: PMC3164740.

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. J Transl Med. 2011 Jun 09; 9:90. Lechner MG, Megiel C, Russell SM, Bingham B, Arger N, Woo T, Epstein AL. PMID: 21658270; PMCID: PMC3128058.

A new mechanism for blocking myeloid-derived suppressor cells by CpG. Clin Cancer Res. 2011 Apr 01; 17(7):1645-8. Lechner MG, Epstein AL. PMID: 21288925; PMCID: PMC4237605.

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. Cancer. 2011 Apr 01; 117(7):1478-89. Lechner MG, Lade S, Liebertz DJ, Prince HM, Brody GS, Webster HR, Epstein AL. PMID: 21425149; PMCID: PMC4175713.

Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol. 2010 Aug 15; 185(4):2273-84. Lechner MG, Liebertz DJ, Epstein AL. PMID: 20644162; PMCID: PMC2923483.

Establishment and characterization of a novel head and neck squamous cell carcinoma cell line USC-HN1. Head Neck Oncol. 2010 Feb 22; 2:5. Liebertz DJ, Lechner MG, Masood R, Sinha UK, Han J, Puri RK, Correa AJ, Epstein AL. PMID: 20175927; PMCID: PMC2841166.

Gene expression in primate liver during viral hemorrhagic fever. Virol J. 2009 Feb 12; 6:20. Djavani M, Crasta OR, Zhang Y, Zapata JC, Sobral B, Lechner MG, Bryant J, Davis H, Salvato MS. PMID: 19216742; PMCID: PMC2657139.

Thyroid Nodules and Cancer in the Elderly. Endotext. 2000. Lechner MG, Hershman JM. View Publication.