{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:18:41Z","timestamp":1788866321572,"version":"build-2803163510"},"reference-count":57,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Despite advances in targeted kinase inhibitor development for patients with medullary thyroid cancer (MTC), most patients develop resistance and would benefit from alternative approaches. Immune-based therapies are now considered for patients with progressive MTC. This study is the first comprehensive assessment of the immune milieu, immune-suppressive molecules, and potential tumor antigens in patients with MTC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Primary and\/or regionally metastatic tumor tissues from 46 patients with MTC were screened for immune infiltrates by using standard immunohistochemistry (IHC) and further analyzed by multispectral imaging for T cell and myeloid markers. RNASeq expression profiling was performed in parallel. RNASeq, targeted sequencing, and IHC techniques identified cancer-associated mutations and MTC-enriched proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Organized immune infiltration was observed in 49% and 90% of primary and metastatic tumors, respectively. CD8\n                      <jats:sup>+<\/jats:sup>\n                      cells were the dominant T cell subtype in most samples, while CD163\n                      <jats:sup>+<\/jats:sup>\n                      macrophages were most frequent among myeloid infiltrates. PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cells were evident in 24% of patients. Myeloid subsets were largely major histocompatibility complex II (MHCII\n                      <jats:sup>\u2212<\/jats:sup>\n                      ), suggesting a dysfunctional phenotype. Expression profiling confirmed enrichment in T cell, macrophage, and inflammatory profiles in a subset of samples. PD-L1 was expressed at low levels in a small subset of patients, while the immune regulatory molecules CD155 and CD47 were broadly expressed. Calcitonin, GRP, HIST1H4E, NOMO3, and NPIPA2 were highly and specifically expressed in MTC. Mutations in tumor suppressors,\n                      <jats:italic toggle=\"yes\">PTEN<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">p53,<\/jats:italic>\n                      and mismatch repair genes,\n                      <jats:italic toggle=\"yes\">MSH2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">MSH6<\/jats:italic>\n                      , may be relevant to disease progression and antigenicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This study suggests that MTC is a more immunologically active tumor that has been previously reported. Patients with advanced MTC should be screened for targetable antigens and immune checkpoints to determine their eligibility for current clinical trials. Additional studies are necessary to fully characterize the antigenic potential of MTC and may encourage the development of adoptive T cells therapies for this rare tumor.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2019.0604","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T06:46:32Z","timestamp":1585896392000},"page":"1263-1279","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":54,"title":["Comprehensive Immune Profiling of Medullary Thyroid Cancer"],"prefix":"10.1177","volume":"30","author":[{"given":"Nikita","family":"Pozdeyev","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Erickson","sequence":"additional","affiliation":[{"name":"Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Ellison","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Rivard","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Sams","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred R.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Denver, Aurora, Colorado, USA."},{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA."},{"name":"University of Colorado Cancer Center, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan R.","family":"Haugen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA."},{"name":"University of Colorado Cancer Center, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jena D.","family":"French","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA."},{"name":"University of Colorado Cancer Center, University of Colorado Denver, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00337-X"},{"key":"e_1_3_5_3_2","unstructured":"Howlader N Noone AM Krapcho M Miller D Bishop K Altekruse SF Kosary CL Yu M Ruhl J Tatalovich Z Mariotto A Lewis DR Chen HS Feuer EJ Cronin KA (eds). 2016 Surveillance Epidemiology and End Results (SEER): Cancer Statistics Review 1975\u20132013. Available at http:\/\/seer.cancer.gov\/csr\/1975_2013\/ based on November 2015 SEER data submission posted to the SEER web site April 2016. (accessed September13 2019)."},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31813e66b9"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22244"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0335"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.4659"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.5040"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197704142961502"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197511)36:5<1658::AID-CNCR2820360519>3.0.CO;2-0"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3892\/or_00000391"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-002-0325-z"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.10.7949"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-013-1505-8"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2292"},{"key":"e_1_3_5_16_2","unstructured":"AJCC. 2002. AJCC Cancer Staging Handbook: TNM Classification of Malignant Tumors. Sixth edition. Springer New York."},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31245"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_5_19_2","unstructured":"Andrews S. FastQC: a quality control tool for high throughput sequence data. Available at: www.bioinformatics.babraham.ac.uk\/projects\/fastqc (accessed September13 2019)."},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.095"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0342"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91190"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.050"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.035600"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0373"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3175"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2004.04.007"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12150"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-016-1947-x"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19840601)53:11<2472::AID-CNCR2820531118>3.0.CO;2-A"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2016-2295"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.11"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2012.0207"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncoscience.161"},{"key":"e_1_3_5_36_2","unstructured":"Dadu R Rodrigues Canales J Wistuba II Tian W Lui H Gurubbs E Cote G Ray G Williams MD Cabanillas ME 2015 Immune markers in medullary thyroid cancer (MTC) and their clinical significance. Abstract presented at the 15th International Thyroid Congress Program and Meeting Lake Buena Vista FL 2015. Abstract no. 491."},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-17-0104"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100637"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199911)29:11<3440::AID-IMMU3440>3.0.CO;2-C"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716435"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-050715-104655"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13324"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2017.02.30"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1385\/EP:12:3:291"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81603"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02486"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-017-2045-4"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.272"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2019.02.008"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251102"},{"key":"e_1_3_5_51_2","doi-asserted-by":"crossref","unstructured":"Yossef R Tran E Deniger DC Gros A Pasetto A Parkhurst MR Gartner JJ Prickett TD Cafri G Robbins PF Rosenberg SA. 2018. Enhanced detection of neoantigen-reactive T cells targeting unique and shared oncogenes for personalized cancer immunotherapy. JCI Insight 3:e122467.","DOI":"10.1172\/jci.insight.122467"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0879"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1632"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0739"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.745448"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-08-0158"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0056"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0378-y"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2019.0604","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2019.0604","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2019.0604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T10:11:40Z","timestamp":1782382300000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2019.0604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,3]]},"references-count":57,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1089\/thy.2019.0604"],"URL":"https:\/\/doi.org\/10.1089\/thy.2019.0604","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,3]]}}}