CONTEXT: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3-5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases. OBJECTIVE: We hypothesized that a T-cell response is generated in advanced thyroid cancer and may be a viable therapeutic target. DESIGN: Primary DTCs were analyzed by quantitative RT-PCR (n = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1, PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were analyzed by immunohistochemistry. SETTING: The study was conducted at the University of Colorado Hospital. PATIENTS: Thyroid cancer patients undergoing thyroidectomy or completion surgery for advanced disease between 2002 and 2013 participated in the study. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURE: Immune markers were analyzed for association with disease severity. RESULTS: Immune markers were commonly expressed at the RNA level. PD-L1 was higher (P = .0443) in patients with nodal metastases. FoxP3(+) (P < .0001), PD-1(+)CD8(+) (P = .0058), and PD-1(+)CD4(+) (P = .0104) T cells were enriched in DTC biopsies. CD8(+) and FoxP3(+) T cells were detected by immunohistochemistry in all pT4 tumors and a subset of metastases. PD-1(+) lymphocytes were found in 50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22 cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373). BRAF(V600E) mutation was associated with higher frequencies of tumor-associated lymphocytes (P = .0095) but not PD-L1 expression. CONCLUSIONS: PD-1 checkpoint blockades may have therapeutic efficacy in patients with aggressive forms of thyroid cancer.
CONTEXT: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3-5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases. OBJECTIVE: We hypothesized that a T-cell response is generated in advanced thyroid cancer and may be a viable therapeutic target. DESIGN: Primary DTCs were analyzed by quantitative RT-PCR (n = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1, PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were analyzed by immunohistochemistry. SETTING: The study was conducted at the University of Colorado Hospital. PATIENTS: Thyroid cancerpatients undergoing thyroidectomy or completion surgery for advanced disease between 2002 and 2013 participated in the study. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURE: Immune markers were analyzed for association with disease severity. RESULTS: Immune markers were commonly expressed at the RNA level. PD-L1 was higher (P = .0443) in patients with nodal metastases. FoxP3(+) (P < .0001), PD-1(+)CD8(+) (P = .0058), and PD-1(+)CD4(+) (P = .0104) T cells were enriched in DTC biopsies. CD8(+) and FoxP3(+) T cells were detected by immunohistochemistry in all pT4 tumors and a subset of metastases. PD-1(+) lymphocytes were found in 50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22 cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373). BRAF(V600E) mutation was associated with higher frequencies of tumor-associated lymphocytes (P = .0095) but not PD-L1 expression. CONCLUSIONS: PD-1 checkpoint blockades may have therapeutic efficacy in patients with aggressive forms of thyroid cancer.
Authors: Andrea Boni; Alexandria P Cogdill; Ping Dang; Durga Udayakumar; Ching-Ni Jenny Njauw; Callum M Sloss; Cristina R Ferrone; Keith T Flaherty; Donald P Lawrence; David E Fisher; Hensin Tsao; Jennifer A Wargo Journal: Cancer Res Date: 2010-06-15 Impact factor: 12.701
Authors: Julie R Brahmer; Charles G Drake; Ira Wollner; John D Powderly; Joel Picus; William H Sharfman; Elizabeth Stankevich; Alice Pons; Theresa M Salay; Tracee L McMiller; Marta M Gilson; Changyu Wang; Mark Selby; Janis M Taube; Robert Anders; Lieping Chen; Alan J Korman; Drew M Pardoll; Israel Lowy; Suzanne L Topalian Journal: J Clin Oncol Date: 2010-06-01 Impact factor: 44.544
Authors: R Houston Thompson; Susan M Kuntz; Bradley C Leibovich; Haidong Dong; Christine M Lohse; W Scott Webster; Shomik Sengupta; Igor Frank; Alexander S Parker; Horst Zincke; Michael L Blute; Thomas J Sebo; John C Cheville; Eugene D Kwon Journal: Cancer Res Date: 2006-04-01 Impact factor: 12.701
Authors: Mojgan Ahmadzadeh; Laura A Johnson; Bianca Heemskerk; John R Wunderlich; Mark E Dudley; Donald E White; Steven A Rosenberg Journal: Blood Date: 2009-05-07 Impact factor: 22.113
Authors: François Ghiringhelli; Pierre E Puig; Stephan Roux; Arnaud Parcellier; Elise Schmitt; Eric Solary; Guido Kroemer; François Martin; Bruno Chauffert; Laurence Zitvogel Journal: J Exp Med Date: 2005-09-26 Impact factor: 14.307
Authors: Katherine D Gray; Jaclyn E McCloskey; Yogindra Vedvyas; Olivia R Kalloo; Steve El Eshaky; Yanping Yang; Enda Shevlin; Marjan Zaman; Timothy M Ullmann; Heng Liang; Dessislava Stefanova; Paul J Christos; Theresa Scognamiglio; Andrew B Tassler; Rasa Zarnegar; Thomas J Fahey; Moonsoo M Jin; Irene M Min Journal: Clin Cancer Res Date: 2020-09-04 Impact factor: 12.531
Authors: Danae A Delivanis; Michael P Gustafson; Svetlana Bornschlegl; Michele M Merten; Lisa Kottschade; Sarah Withers; Allan B Dietz; Mabel Ryder Journal: J Clin Endocrinol Metab Date: 2017-08-01 Impact factor: 5.958