Please confirm you are human (Sign Up for free to never see this)
← Back to Search
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
Trevor E Angell, M. G. Lechner, Julie Jang, J. Lopresti, A. Epstein
Published 2014 · Biology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
Purpose: To evaluate MHC class I expression on papillary thyroid cancer (PTC) and analyze changes in MHC expression and associated immune activation with current and experimental treatments for thyroid cancer using in vitro PTC cell lines. Experimental Design: MHC class I expression and assessment of tumor-infiltrating leukocyte populations were evaluated by immunohistochemistry. PTC cell lines were analyzed for HLA-ABC expression by flow cytometry following tyrosine kinase inhibitor, IFNα or IFNγ, or radiation treatment. Functional changes in antigenicity were assessed by coculture of allogeneic donor peripheral blood leukocytes (PBL) with pretreated or untreated PTC cell lines and measurement of T-cell activation and cytokine production. Results: Both MHC class I and β2-microglobulin expression was reduced or absent in 76% of PTC specimens and was associated with reduced tumor-infiltrating immune cells, including effector (CD3+, CD8+, CD16+) and suppressor (FoxP3+) populations. Treatment of PTC cell lines with the MEK1/2 inhibitor selumetinib or IFN increased HLA-ABC expression. This phenotypic change was associated with increased T-cell activation (%CD25+ of CD3+) and IL2 production by PBL cocultured with treated PTC cell lines. Additive effects were seen with combination selumetinib and IFN treatment. Conclusions: MHC class I expression loss is frequent in human PTC specimens and represents a significant mechanism of immune escape. Increased antigenicity following selumetinib and IFN treatment warrants further study for immunotherapy of progressive PTC. Clin Cancer Res; 20(23); 6034–44. ©2014 AACR.
This paper references
Interferon induced thyroiditis.
Y. Tomer (2009)
Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion
R. Schreiber (2011)
Differentiated thyroid cancer is associated with less aggressive disease and better outcome in patients with coexisting Hashimotos thyroiditis.
S. Dvorkin (2013)
December 1, 2014 Clinical Cancer Research 6044 Angell et al. on April 3
Single institution experience with recombinant gamma-interferon in the treatment of patients with metastatic renal cell carcinoma.
S. Mani (1996)
The evolving field of tyrosine kinase inhibitors in the treatment of endocrine tumors.
L. Ye (2010)
Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events.
J. Weber (2007)
How tumours escape mass destruction
T. Stewart (2008)
Improving the therapeutic index of IL-2.
D. McDermott (2010)
Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005
A. Chen (2009)
Generation of human interferon gamma and tumor Necrosis factor alpha chimeric TNT-3 fusion proteins.
J. Sharifi (2002)
December 1, 2014 Clinical Cancer Research 6044 Angell et al. on April 15
Chemokines, costimulatory molecules and fusion proteins for the immunotherapy of solid tumors.
M. G. Lechner (2011)
Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype.
C. Garbe (1990)
Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma.
S. Russell (2013)
Differentiated thyroid cancer is associated with less aggressive disease and better outcome in patients with coexisting Hashimoto's thyroiditis
S Dvorkin (2013)
Indoleamine 2,3-dioxygenase 1 (IDO1) is up-regulated in thyroid carcinoma and drives the development of an immunosuppressant tumor microenvironment.
S. Moretti (2014)
Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy
E. Reits (2006)
BRAF V600E in papillary thyroid carcinoma is associated with increased programmed death ligand 1 expression and suppressive immune cell infiltration.
Trevor E Angell (2014)
Analysis of the MHC Class I Antigen Presentation Machinery in Human Embryonal Carcinomas: Evidence for Deficiencies in TAP, LMP and MHC Class I Expression and their Upregulation by IFN‐γ
B. Seliger (1997)
Gene Signature in Melanoma Associated With Clinical Activity: A Potential Clue to Unlock Cancer Immunotherapy
T. Gajewski (2010)
Clin Cancer Res Clinical Cancer Research
Papillary Thyroid Carcinoma Managed at the Mayo Clinic during Six Decades (1940–1999): Temporal Trends in Initial Therapy and Long-term Outcome in 2444 Consecutively Treated Patients
I. Hay (2002)
Expression of ICAM-1, B7.1 and TPO on human thyrocytes induced by IFN-alpha.
X. You (1999)
Molecular profiling to identify relevant immune resistance mechanisms in the tumor microenvironment.
T. Gajewski (2011)
Interferon-gamma induces HLA-DR expression by thyroid epithelium.
Ian Todd (1985)
Jang is a TL1 Trainee awarded under the TL1 (pre-doctoral) Training Award through Southern California Clinical and Translational Science Institute at University of Southern California
Thyroiditis after treatment with interleukin-2 and interferon alpha-2a.
G. Pichert (1990)
“Hard” and “soft” lesions underlying the HLA class I alterations in cancer cells: Implications for immunotherapy
F. Garrido (2010)
Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation.
L. Cunha (2013)
Grant Support This work was supported by NIH grants 3T32GM067587-07S1 (to M.G. Lechner) and P30CA014089
Chimeric TNT-3 antibody/murine interferon-gamma fusion protein for the immunotherapy of solid malignancies.
M. Mizokami (2003)
Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.
D. Cooper (2009)
Infiltration of amixture of different immune cells may be related to molecular profile of differentiated thyroid cancer
LL Cunha (2012)
Infiltration of a mixture of immune cells may be related to good prognosis in patients with differentiated thyroid carcinoma
L. Cunha (2012)
Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer.
Mabel M Ryder (2008)
Targeting MAPK Signaling in Melanoma Cells : Implications for Immune Recognition and Cell Fate
Stefan Massen (2010)
Modulation of major histocompatibility complex Class I molecules and major histocompatibility complex-bound immunogenic peptides induced by interferon-alpha and interferon-gamma treatment of human glioblastoma multiforme.
I. Yang (2004)
A phase I trial of recombinant gamma interferon in patients with cancer
K. Foon (2004)
Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines reveals cross-contamination resulting in cell line redundancy and misidentification.
R. Schweppe (2008)
Tumor-associated lymphocytes and increased FoxP3+ regulatory T cell frequency correlate with more aggressive papillary thyroid cancer.
J. French (2010)
Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas
L. Cunha (2012)
RNA sequencing identifies multiple fusion transcripts, differentially expressed genes, and reduced expression of immune function genes in BRAF (V600E) mutant vs BRAF wild-type papillary thyroid carcinoma.
R. Smallridge (2014)
Cancer statistics, 2013
R. Siegel (2013)
Phase II Efficacy and Pharmacogenomic Study of Selumetinib (AZD6244; ARRY-142886) in Iodine-131 Refractory Papillary Thyroid Carcinoma with or without Follicular Elements
D. Hayes (2012)
Epstein is a co-founder
MHC antigens and tumor escape from immune surveillance.
F. Garrido (2001)
Changes of apoptosis, p53, and bcl-2 by irradiation in poorly differentiated thyroid carcinoma cell lines: a prognostic marker for the prospect of therapeutic success?
F. Pohl (2010)
Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy.
M. Callahan (2010)
Molecular Mechanisms of IFN-γ to Up-Regulate MHC Class I Antigen Processing and Presentation
F. Zhou (2009)
Implications for immunosurveillance of altered HLA class I phenotypes in human tumours.
F. Garrido (1997)
Phenotypical analysis of lymphocytes with suppressive and regulatory properties (Tregs) and NK cells in the papillary carcinoma of thyroid.
F. Gogali (2012)
American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid
DS Cooper (2009)
HLA Expression in PTC www.aacrjournals.org Clin Cancer Res
Mutations of the BRAF gene in human cancer
Helen Davies (2002)
N. Dubrawsky (1989)
High-dose Interleukin-2 Can Produce a High Rate of Response and Durable Remissions in Appropriately Selected Patients With Metastatic Renal Cancer
A. Shablak (2011)
Review : antiCTLA - 4 antibody ipilimumab : case studies of clinical response and immunerelated adverse events
J Weber (2007)
MHC class I antigens and immune surveillance in transformed cells.
N. Aptsiauri (2007)
Immunogenicity of Murine Solid Tumor Models as a Defining Feature of In Vivo Behavior and Response to Immunotherapy
M. G. Lechner (2013)
The immune score as a new possible approach for the classification of cancer
J. Galon (2011)
Infiltration of a mixture of different immune cells may be related to molecular profile of differentiated thyroid cancer.
L. Cunha (2012)
This paper is referenced by
Novel targeted therapies and immunotherapy for advanced thyroid cancers
G. Naoum (2018)
MHC Class-I Loss and Cancer Immune Escape
Dr. Federico Garrido (2019)
Regulation of Cancer Immune Checkpoints: Molecular and Cellular Mechanisms and Therapy
J. Xu (2020)
PD-L1 Expression Level Displays a Positive Correlation with Immune Response in Pancreatic Cancer
L. Zhao (2020)
The mechanisms tumor cells utilize to evade the host's immune system.
Nyanbol Kuol (2017)
Regulation of cancer-specific miRNAs by MDA-7/IL-24
Danielle Scheunemann (2019)
Intracellular targets as source for cleaner targets for the treatment of solid tumors.
H. Gerber (2019)
Quantifying Antigen-Specific T Cell Responses When Using Antigen-Agnostic Immunotherapies
Jacob P van Vloten (2019)
The transition from HLA-I positive to HLA-I negative primary tumors: the road to escape from T-cell responses.
N. Aptsiauri (2018)
Immune checkpoint blockade as a potential therapeutic target in non-small cell lung cancer
J. Yang (2016)
MHC/HLA Class I Loss in Cancer Cells.
F. Garrido (2019)
Leveraging the immune system to treat advanced thyroid cancers.
J. French (2017)
Antigen processing and immune regulation in the response to tumours
E. Reeves (2017)
Inhibition of BRAF Sensitizes Thyroid Carcinoma to Immunotherapy by Enhancing TsMHC-II-mediated Immune Recognition.
Jingtai Zhi (2020)
Expression of classical HLA class I molecules: regulation and clinical impacts
C. René (2016)
T cell receptor mimic antibodies for cancer therapy
Leonid Dubrovsky (2016)
Immunological Mechanisms Underneath the Efficacy of Cancer Therapy
L. Galluzzi (2016)
High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China
Fang-Fang Shen (2019)
The Graft-Versus-Leukemia Effect in AML
C. Sweeney (2019)
The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture
F. Garrido (2017)
Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases
Gunjan Kak (2018)
NLRC5: new cancer buster?
Feng Tang (2020)
Recent Advances in Polymeric Nanomedicines for Cancer Immunotherapy.
E. Lee (2019)
IL-2 enhanced MHC class I expression in papillary thyroid cancer with Hashimoto's thyroiditis overcomes immune escape in vitro
J. Hu (2020)
Genomic analysis of head and neck endocrine glands
Katayoon Kasaian (2015)
SHP2 negatively regulates HLA-ABC and PD-L1 expression via STAT1 phosphorylation in prostate cancer cells.
Zhuqing Liu (2017)
DNA vaccines, electroporation and their applications in cancer treatment
Si-Hyeong Lee (2015)
THERAPY OF ENDOCRINE DISEASE: Immunotherapy of advanced thyroid cancer: from bench to bedside.
S. Moretti (2020)
Antitumor Activity of BRAF Inhibitor and IFNα Combination in BRAF-Mutant Melanoma.
F. Sabbatino (2016)
Estrogens impair antitumor immunity by promoting the accumulation of myeloid-derived suppressor cells
Nikolaos Svoronos (2016)
Characterization of genomic alterations in CIITA and their functional and clinical implications in malignant lymphomas
A. Mottok (2017)
Interleukins in Thyroid Cancer: From Basic Researches to Applications in Clinical Practice
Chuang Xi (2020)See more