-Tumor Immunology and Immuno-oncology
-Thyroid Cancer
My current research focuses on defining the role of the immune response in advanced thyroid cancers. Using archival and fresh surgical samples. I was the first to characterize PD-1+ T cells and T cell exhaustion in differentiated thyroid cancers. In the past few years, I have published my key data describing partial T exhaustion in regional lymph node metastases (Severson et al., CIR 2015) and the immune response in invasive and distant metastatic disease (Bastman et al., JCEM 2016).
These studies led to our current clinical trial investigating the efficacy of pembrolizumab (anti-PD-1; Merck) in combination with lenvatinib (TKI, VEGFR inhibitor; Eisai) in patients with radioiodine resistant, locally invasive and/or metastatic differentiated thyroid cancer (Opened April 2018; P.I. Dr. Bryan Haugen). Correlative research studies are underway to identify biomarkers of response and resistance to treatment.
In parallel, we are investigating this and other novel combination therapies in a mouse model of advanced thyroid cancer. These studies are applicable across cancer types where patients fail to generate a durable response to antiangiogenic and checkpoint inhibitor combination approaches.
Publications
Bertol BC, Bales ES, Calhoun JD, Mayberry A, Ledezma ML, Sams SB, Orlicky DJ, Donadi EA, Haugen BR, French JD. Lenvatinib Plus Anti-PD-1 Combination Therapy for Advanced Cancers: Defining Mechanisms of Resistance in an Inducible Transgenic Model of Thyroid Cancer. Thyroid. 2022 Jan 12. [Epub ahead of print] PubMed PMID: 34641722
Pozdeyev N, Erickson TA, Zhang L, Ellison K, Rivard CJ, Sams S, Hirsch FR, Haugen BR, French JD. Comprehensive Immune Profiling of Medullary Thyroid Cancer. Thyroid. 2020 Sep;30(9):1263-1279. PubMed PMID: 32242507
French JD. Immunotherapy for advanced thyroid cancers - rationale, current advances and future strategies. Nat Rev Endocrinol. 2020 Nov;16(11):629-641. PubMed PMID: 32839578
Development of an Adrenocortical Cancer Humanized Mouse Model to Characterize Anti-PD1 Effects on Tumor Microenvironment. Lang J, Capasso A, Jordan KR, French JD, Kar A, Bagby SM, Barbee J, Yacob BW, Head LS, Tompkins KD, Freed BM, Somerset H, Clark TJ, Pitts TM, Messersmith WA, Eckhardt SG, Wierman ME, Leong S, Kiseljak-Vassiliades K. J Clin Endocrinol Metab. 2020 Jan 1;105(1). PMID: 31513709
Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S, French JD, Borre PV, LaBarbera DV, Tan AC, Schweppe RE, Fishbein L, Ross JS, Haugen BR, Bowles DW. Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers. Clin Cancer Res. 2018 Jul 1;24(13):3059-3068. PubMed PMID: 29615459
French JD, Haugen BR. Thyroid cancer: CAR T cell therapy - potential in advanced thyroid cancer?. Nat Rev Endocrinol. 2018 Jan;14(1):10-11. PubMed PMID: 29170541
French JD, Haugen BR. Thyroid-Specific T Cells in Patients With Differentiated Thyroid Cancer: Implications for Immune-Based Therapies?. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2131-2132. PubMed PMID: 28899074
French JD, Bible K, Spitzweg C, Haugen BR, Ryder M. Leveraging the immune system to treat advanced thyroid cancers. Lancet Diabetes Endocrinol. 2017 Jun;5(6):469-481. PubMed PMID: 27773653
French JD, Bible K, Spitzweg C, Haugen BR, Ryder M. Leveraging the immune system to treat advanced thyroid cancers. Lancet Diabetes Endocrinol. 2016 Oct 20. [Epub ahead of print] PubMed PMID: 27773653
Bastman JJ, Serracino HS, Zhu Y, Koenig MR, Mateescu V, Sams SB, Davies KD, Raeburn CD, McIntyre RC Jr, Haugen BR, French JD. Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer. J Clin Endocrinol Metab. 2016 Jul;101(7):2863-73. PubMed PMID: 27045886
16. Severson JJ, Serracino HS, Mateescu V, Raeburn CD, McIntyre RC, Sams SB, Haugen BR, French JD. PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer. Cancer Immunol Res. 2015 Feb 19. pii: canimm.0201.2014. [Epub ahead of print] PMID: 25701326
J.D. French. Revisiting Immune-based Therapies for Aggressive Follicular Cell-Derived Thyroid Cancers. Thyroid, 2013; 23(5):529-42. Epub 2013 April 18. PMID: 23317509
T.C.Bruno, J.D. French, K.R. Jordan, O. Ramirez, T.R. Sippel, V.F. Borges, B.R. Haugen, M.D. McCarter, A. Waziri, J.E. Slansky. Influence of Human Immune Cells on Cancer: Studies at the University of Colorado. Immunol Res, 2013; 55(1): 22-33. Epub 2012 Sep 1. PMID: 22941561
Jena D. French, Gregory R. Kotnis, Sherif Said, Christopher D. Raeburn, Robert C. McIntyre, Jr., Joshua P. Klopper, Bryan R. HaugenProgrammed Death-1+ T Cells and Regulatory T Cells are Enriched in Tumor-Involved Lymph Nodes and Associated with Aggressive Features in Papillary Thyroid Cancer. JCEM, in revision.
T.C.Bruno, J.D. French, K.R. Jordan, O. Ramirez, T.R. Sippel, V.F. Borges, B.R. Haugen, M.D. McCarter, A. Waziri, J.E. Slansky. Influence of human immune cells on cancer: studies at the University of Colorado.
Immunol Res. 2012 Sep 1(review). [Epub ahead of print] PMID: 22941561
J.D. French, G.R. Kotnis, M.S. Said, C.D. Raeburn, R.C. McIntyre, Jr., J.P. Klopper, B.R. Haugen. Programmed Death-1+ T Cells and Regulatory T Cells are Enriched in Tumor-Involved Lymph Nodes and Associated with Aggressive Features in Papillary Thyroid Cancer. JCEM, 2012; 97(6): E934-43. Epub 2012 March 30. PMID: 22466343
J.D. French. Revisiting Immune-based Therapies for Aggressive Follicular Cell-Derived Thyroid Cancers. Thyroid. Epub 2012 January 17, in press (review).
J.D. French, Z.J. Weber, D.L. Fretwell, M.S. Said, J.P. Klopper, and B.R. Haugen. Tumor-Associated Lymphocytes and Increased FoxP3+ Regulatory T Cell Frequency Correlate with More Aggressive Papillary Thyroid Cancer. JCEM, in press.
J.D. French, Z.J. Weber, D.L. Fretwell, M.S. Said, J.P. Klopper, and B.R. Haugen. Tumor-Associated Lymphocytes and Increased FoxP3+ Regulatory T Cell Frequency Correlate with More Aggressive Papillary Thyroid Cancer. JCEM, 2010; 95: 2325-2333.
J. D. French, C. L. Roark, W. K. Born, and R. L. O’Brien. Gamma-delta T cell homeostasis is negatively regulated by beta-2 microglobulin. J. Immunol., 2009; 182(4): 1892-1900.