{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:11:17Z","timestamp":1787242277734,"version":"build-2736575974"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The immune microenvironment profoundly shapes the progression and therapeutic response of thyroid carcinoma. Through comprehensive analysis of single-cell RNA sequencing data, this review delineates the immune landscapes of papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinomas (PDTC), and anaplastic thyroid carcinomas (ATC), revealing a differentiation dependent trajectory of tumor immune microenvironment remodeling\u2014from immune activation suppression coexistence in PTC, to immune exclusion in PDTC, and terminal exhaustion in ATC. This single-cell based approach enables high resolution dissection of cellular heterogeneity, immune crosstalk, and spatial organization that are often masked in bulk analyses. Such insights provide a scientific basis for precision immunotherapy, offering guidance for differentiation tailored strategies to overcome immune escape and improve clinical outcomes in thyroid cancer.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1738583","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T06:38:33Z","timestamp":1767595113000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Single-cell sequencing reveals the tumor immune microenvironment in thyroid cancer: a narrow review"],"prefix":"10.3389","volume":"16","author":[{"given":"Kangcong","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gengluan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xidi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Xun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefeng","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA: A Cancer J Clin"},{"key":"B2","article-title":"Dedifferentiation patterns in DTC: is PDTC an intermediate state between DTC and ATC","volume":"12","author":"Wen","year":"2019","journal-title":"Int J Clin Exp Pathol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2010.03.013","article-title":"Anaplastic thyroid carcinoma: pathogenesis and emerging therapies","volume":"22","author":"Smallridge","year":"2010","journal-title":"Clin Oncol (R Coll Radiol)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.k06-166","article-title":"Clinical features and prognostic factors for survival in patients with poorly differentiated thyroid carcinoma and comparison to the patients with the aggressive variants of papillary thyroid carcinoma","volume":"54","author":"Jung","year":"2007","journal-title":"Endocr J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-014-0082-9","article-title":"The effect of immune microenvironment on the progression and prognosis of colorectal cancer","volume":"31","author":"Chen","year":"2014","journal-title":"Med Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of cancer: new dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.7150\/jca.44506","article-title":"Immune microenvironment of thyroid cancer","volume":"11","author":"Yin","year":"2020","journal-title":"J Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","article-title":"Macrophage diversity enhances tumor progression and metastasis","volume":"141","author":"Qian","year":"2010","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049","article-title":"Massively parallel digital transcriptional profiling of single cells","volume":"8","author":"Zheng","year":"2017","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"6058","DOI":"10.1038\/s41467-021-26343-3","article-title":"Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma","volume":"12","author":"Pu","year":"2021","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e173712","DOI":"10.1172\/jci.insight.173712","article-title":"A distinct tumor microenvironment makes anaplastic thyroid cancer more lethal but immunotherapy sensitive than papillary thyroid cancer","volume":"9","author":"Han","year":"2024","journal-title":"JCI Insight"},{"key":"B13","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1186\/s12935-021-02084-7","article-title":"The immune landscape of the microenvironment of thyroid cancer is closely related to differentiation status","volume":"21","author":"Cunha","year":"2021","journal-title":"Cancer Cell Int"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4227","article-title":"Tumor-infiltrating T cells and the PD-1 checkpoint pathway in advanced differentiated and anaplastic thyroid cancer","volume":"101","author":"Bastman","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e240169","DOI":"10.1530\/erc-24-0169","article-title":"Persistent pre-exhausted CD8+ T cells shape the tumor immune microenvironment in anaplastic thyroid cancer","volume":"32","author":"Ruan","year":"2025","journal-title":"Endocr Relat Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13046-025-03341-7","article-title":"Single-cell transcriptomics analysis reveals that the tumor-infiltrating B cells determine the indolent fate of papillary thyroid carcinoma","volume":"44","author":"Li","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2404491","DOI":"10.1002\/advs.202404491","article-title":"Spatial and single-cell transcriptomics unraveled spatial evolution of papillary thyroid cancer","volume":"12","author":"Zheng","year":"2025","journal-title":"Advanced Science"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01167","article-title":"Immune profiling of thyroid carcinomas suggests the existence of two major phenotypes: an ATC-like and a PDTC-like","volume":"104","author":"Giannini","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3601","DOI":"10.1038\/s41467-025-58910-3","article-title":"Integrative proteogenomic characterization reveals therapeutic targets in poorly differentiated and anaplastic thyroid cancers","volume":"16","author":"Pan","year":"2025","journal-title":"Nat Commun"},{"key":"B20","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s12943-022-01658-x","article-title":"CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment","volume":"21","author":"Pan","year":"2022","journal-title":"Mol Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2405399","DOI":"10.1002\/advs.202405399","article-title":"CCL20\/CXCL5 drives crosstalk between anaplastic thyroid cancer stem cells and tumor-associated macrophages to promote tumor progression","volume":"12","author":"Liu","year":"2025","journal-title":"Advanced Science"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2008.0237","article-title":"The expression of monocyte chemotactic protein-1 in papillary thyroid carcinoma is correlated with lymph node metastasis and tumor recurrence","volume":"19","author":"Tanaka","year":"2009","journal-title":"Thyroid"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.154495","article-title":"Inflammatory tumor microenvironment of thyroid cancer promotes cellular dedifferentiation and silencing of iodide-handling genes expression","volume":"246","author":"Zhang","year":"2023","journal-title":"Pathol Res Pract"},{"key":"B24","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1007\/s12672-024-00904-6","article-title":"Current and future of immunotherapy for thyroid cancer based on bibliometrics and clinical trials","volume":"15","author":"Wang","year":"2024","journal-title":"Discov Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2791","article-title":"Cross-talk between tumor and endothelial cells involving the Notch3-Dll4 interaction marks escape from tumor dormancy","volume":"69","author":"Indraccolo","year":"2009","journal-title":"Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.671787","article-title":"Parathyroid changes after RAI in patients with differentiated thyroid carcinoma","volume":"12","author":"Xiao","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.7675","article-title":"TERT promoter mutations and their correlation with BRAF and RAS mutations in a consecutive cohort of 145 thyroid cancer cases","volume":"15","author":"Insilla","year":"2018","journal-title":"Oncol Lett"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e250015","DOI":"10.1530\/ec-25-0015","article-title":"Retinoid X receptor \u03b3 regulates epithelial-mesenchymal transition and tumor immune infiltration in papillary thyroid cancer tumorigenesis: an experimental and in silico study","volume":"14","author":"Li","year":"2025","journal-title":"Endocr Connect"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.840811","article-title":"Single-cell transcriptome analysis reveals inter-tumor heterogeneity in bilateral papillary thyroid carcinoma","volume":"13","author":"Wang","year":"2022","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"18125","DOI":"10.1038\/s41598-024-69187-9","article-title":"The role of immune cells and immune related genes in the tumor microenvironment of papillary thyroid cancer and their significance for immunotherapy","volume":"14","author":"Li","year":"2024","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1438235","article-title":"Immune microenvironment in papillary thyroid carcinoma: roles of immune cells and checkpoints in disease progression and therapeutic implications","volume":"15","author":"Zheng","year":"2024","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.894919","article-title":"Immune profiling identifies CD8(+) T-cell subset signatures as prognostic markers for recurrence in papillary thyroid cancer","volume":"13","author":"Chen","year":"2022","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e008983","DOI":"10.1136\/jitc-2024-008983","article-title":"Interactions between LAMP3+ dendritic cells and T-cell subpopulations promote immune evasion in papillary thyroid carcinoma","volume":"12","author":"Wang","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI169653","article-title":"Anaplastic transformation in thyroid cancer revealed by single-cell transcriptomics","volume":"133","author":"Lu","year":"2023","journal-title":"J Clin Invest"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.570604","article-title":"Immune cell confrontation in the papillary thyroid carcinoma microenvironment","volume":"11","author":"Xie","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-012-9853-2","article-title":"Regulatory T cells and plasmacytoid dendritic cells contribute to the immune escape of papillary thyroid cancer coexisting with multinodular non-toxic goiter","volume":"44","author":"Yu","year":"2013","journal-title":"Endocrine"},{"key":"B37","doi-asserted-by":"publisher","first-page":"192","DOI":"10.3803\/EnM.2013.28.3.192","article-title":"The expression of tumor-associated macrophages in papillary thyroid carcinoma","volume":"28","author":"Kim","year":"2013","journal-title":"Endocrinol Metab"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-4418-7","article-title":"TNF-\u03b1 increases the membrane expression of the chemokine receptor CCR6 in thyroid tumor cells, but not in normal thyrocytes: potential role in the metastatic spread of thyroid cancer","volume":"37","author":"Coperchini","year":"2016","journal-title":"Tumour Biol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3175","DOI":"10.1038\/s41467-024-47581-1","article-title":"Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks","volume":"15","author":"Qu","year":"2024","journal-title":"Nat Commun"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1038\/s41598-020-80694-3","article-title":"Potential role of M2 TAMs around lymphatic vessels during lymphatic invasion in papillary thyroid carcinoma","volume":"11","author":"Kabasawa","year":"2021","journal-title":"Sci Rep"},{"key":"B41","doi-asserted-by":"publisher","first-page":"130","DOI":"10.3892\/ol.2025.14876","article-title":"Single\u2212cell transcriptomic analysis revealed the tumor\u2212associated microenvironment of papillary thyroid carcinoma with metastasis","volume":"29","author":"Zhang","year":"2025","journal-title":"Oncol Lett"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1101\/2021.02.24.21251881","article-title":"Single-cell RNA sequencing reveals a novel cell type and immunotherapeutic targets in papillary thyroid cancer","author":"Wang","year":"2021","journal-title":"medRxiv"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01859","article-title":"Prostaglandin E2 secreted by thyroid cancer cells contributes to immune escape through the suppression of natural killer (NK) cell cytotoxicity and NK cell differentiation","volume":"9","author":"Park","year":"2018","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1053137","article-title":"Exercise-induced IL-15 acted as a positive prognostic implication and tumor-suppressed role in pan-cancer","volume":"13","author":"Luo","year":"2022","journal-title":"Front Pharmacol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-023-02072-w","article-title":"B cells and tertiary lymphoid structures are associated with survival in papillary thyroid cancer","volume":"46","author":"Li","year":"2023","journal-title":"J Endocrinol Invest"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.09.042","article-title":"Human regulatory B cells control the T(FH) cell response","volume":"140","author":"Achour","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-21-0414","article-title":"Translating the immune microenvironment of thyroid cancer into clinical practice","volume":"29","author":"Cunha","year":"2022","journal-title":"Endocr Relat Cancer"},{"key":"B48","doi-asserted-by":"publisher","first-page":"eadm8660","DOI":"10.1126\/sciadv.adm8660","article-title":"Targeting conserved TIM3(+)VISTA(+) tumor-associated macrophages overcomes resistance to cancer immunotherapy","volume":"10","author":"Vanmeerbeek","year":"2024","journal-title":"Sci Adv"},{"key":"B49","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.cell.2019.02.005","article-title":"Unleashing type-2 dendritic cells to drive protective antitumor CD4(+) T cell immunity","volume":"177","author":"Binnewies","year":"2019","journal-title":"Cell"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-020-05898-9","article-title":"Poorly differentiated thyroid carcinoma (PDTC) characteristics and the efficacy of radioactive iodine (RAI) therapy as an adjuvant treatment in a tertiary cancer care center","volume":"277","author":"Thiagarajan","year":"2020","journal-title":"Eur Arch Oto-Rhino-Laryngology"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2006.02712.x","article-title":"Clinical characteristics of poorly differentiated thyroid carcinomas compared with those of classical papillary thyroid carcinomas","volume":"66","author":"Lin","year":"2007","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85271","article-title":"Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers","volume":"126","author":"Landa","year":"2016","journal-title":"J Clin Invest"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-022-03179-5","article-title":"Integrated analysis of novel macrophage related signature in anaplastic thyroid cancer","volume":"78","author":"Luo","year":"2022","journal-title":"Endocrine"},{"key":"B54","doi-asserted-by":"publisher","first-page":"553","DOI":"10.3892\/ol.2021.12814","article-title":"PD-L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study","volume":"22","author":"Cameselle-Garcia","year":"2021","journal-title":"Oncol letters"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e191781","DOI":"10.1101\/2025.01.27.635086","article-title":"Loss of tumor cell MHC class II drives insensitivity of BRAF-mutant anaplastic thyroid cancers to MAPK inhibitors","volume":"135","author":"Tiedje","year":"2025","journal-title":"bioRxiv"},{"key":"B56","doi-asserted-by":"publisher","first-page":"e000698","DOI":"10.1136\/jitc-2020-000698","article-title":"Combining BRAF inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of BRAF-mutant thyroid cancer","volume":"8","author":"Crespo-Rodriguez","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2071-9","article-title":"Gasdermin E suppresses tumour growth by activating anti-tumour immunity","volume":"579","author":"Zhang","year":"2020","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"publisher","first-page":"e005538","DOI":"10.1136\/jitc-2022-005538","article-title":"Preconditioning of the immune system modulates the response of papillary thyroid cancer to immune checkpoint inhibitors","volume":"10","author":"Pani","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-005595","article-title":"TLR agonists promote ERK-mediated preferential IL-10 production of regulatory dendritic cells (diffDCs), leading to NK-cell activation","volume":"108","author":"Qian","year":"2006","journal-title":"Blood"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-08-0036","article-title":"Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer","volume":"15","author":"Ryder","year":"2008","journal-title":"Endocr Relat Cancer"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.6.4","article-title":"Inhibiting NF-kappaB signaling activation reduces retinal neovascularization by promoting a polarization shift in macrophages","volume":"61","author":"Sui","year":"2020","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"e54302","DOI":"10.1371\/journal.pone.0054302","article-title":"Genetic and pharmacological targeting of CSF-1\/CSF-1R inhibits tumor-associated macrophages and impairs BRAF-induced thyroid cancer progression","volume":"8","author":"Ryder","year":"2013","journal-title":"PloS One"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2004.11.002","article-title":"Exosomes secreted from monocyte-derived dendritic cells support in vitro naive CD4+ T cell survival through NF-\u03baB activation","volume":"231","author":"Matsumoto","year":"2004","journal-title":"Cell Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.31.2228","article-title":"Semi-vioxanthin isolated from marine-derived fungus regulates tumor necrosis factor-alpha, cluster of differentiation (CD) 80, CD86, and major histocompatibility complex class II expression in RAW264.7 cells via nuclear factor-kappaB and mitogen-activated protein kinase signaling pathways","volume":"31","author":"Yang","year":"2008","journal-title":"Biol Pharm Bull"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.637826","article-title":"Immune landscape of thyroid cancers: new insights","volume":"11","author":"Menicali","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B66","article-title":"Thyroid cancer resistance to chemotherapeutic drugs via autocrine production of interleukin-4 and interleukin-10","volume":"63","author":"Stassi","year":"2003","journal-title":"Cancer Res"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2012.0560","article-title":"CD3\u2013 CD16\u2013 CD56bright immunoregulatory NK cells are increased in the tumor microenvironment and inversely correlate with advanced stages in patients with papillary thyroid cancer","volume":"23","author":"Gogali","year":"2013","journal-title":"Thyroid"},{"key":"B68","volume-title":"DNA repair SNPs as genetic modulators of individual susceptibility to differentiated thyroid cancer and response to radioiodine therapy","author":"Santos","year":"2021"},{"key":"B69","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41419-020-03294-z","article-title":"A new risk factor indicator for papillary thyroid cancer based on immune infiltration","volume":"12","author":"Yang","year":"2021","journal-title":"Cell Death Dis"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012578","article-title":"Cell component and function of tumor microenvironment in thyroid cancer","volume":"23","author":"Shin","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B71","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/cncy.21494","article-title":"Fine-needle aspiration biopsy of secondary neoplasms of the thyroid gland: a multi-institutional study of 62 cases","volume":"123","author":"Pusztaszeri","year":"2015","journal-title":"Cancer Cytopathol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s12022-018-9514-y","article-title":"PD-L1 and IDO1 are expressed in poorly differentiated thyroid carcinoma","volume":"29","author":"Rosenbaum","year":"2018","journal-title":"Endocr Pathol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061405","article-title":"PD-1 ligand expression in epithelial thyroid cancers: potential clinical implications","volume":"20","author":"Ulisse","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184413","article-title":"Immune and inflammatory cells in thyroid cancer microenvironment","volume":"20","author":"Ferrari","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15102863","article-title":"Crosstalk between thyroid carcinoma and tumor-correlated immune cells in the tumor microenvironment","volume":"15","author":"Song","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B76","volume-title":"Exploring tumor macrophage interaction in anaplastic thyroid cancer","author":"Eduardo","year":"2019"},{"key":"B77","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/s12951-025-03223-2","article-title":"Efficient delivery of anlotinib and radioiodine by long circulating nano-capsules for active enhanced suppression of anaplastic thyroid carcinoma","volume":"23","author":"Zhang","year":"2025","journal-title":"J Nanobiotechnology"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113826","article-title":"The genomic and evolutionary landscapes of anaplastic thyroid carcinoma","volume":"43","author":"Zeng","year":"2024","journal-title":"Cell Rep"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102043","article-title":"A spatially resolved transcriptome landscape during thyroid cancer progression","volume":"6","author":"Liao","year":"2025","journal-title":"Cell Rep Med"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2023.100409","article-title":"Molecular signature incorporating the immune microenvironment enhances thyroid cancer outcome prediction","volume":"3","author":"Xu","year":"2023","journal-title":"Cell Genom"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1365055","article-title":"Research progress of immunotherapy against anaplastic thyroid cancer","volume":"14","author":"Chen","year":"2024","journal-title":"Front Oncol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-023-00663-6","article-title":"Integrative single-cell transcriptome analysis reveals immune suppressive landscape in the anaplastic thyroid cancer","volume":"30","author":"Feng","year":"2023","journal-title":"Cancer Gene Ther"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0292-x","article-title":"CellPhoneDB: inferring cell\u2013cell communication from combined expression of multi-subunit ligand\u2013receptor complexes","volume":"15","author":"Efremova","year":"2020","journal-title":"Nat Protoc"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"B86","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nrclinonc.2016.217","article-title":"Tumour-associated macrophages as treatment targets in oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat Rev Clin Oncol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00547-1","article-title":"A timeline of tumour-associated macrophage biology","volume":"23","author":"Cassetta","year":"2023","journal-title":"Nat Rev Cancer"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.02727","article-title":"PD-1 blockade in anaplastic thyroid carcinoma","volume":"38","author":"Capdevila","year":"2020","journal-title":"J Clin Oncol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.02.015","article-title":"Macrophages and therapeutic resistance in cancer","volume":"27","author":"Ruffell","year":"2015","journal-title":"Cancer Cell"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2024.0266","article-title":"Transcriptome of anaplastic thyroid cancer reveals two molecular subtypes with distinct tumor microenvironment and prognosis","volume":"35","author":"Byun","year":"2025","journal-title":"Thyroid"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.01.008","article-title":"Role of macrophage targeting in the antitumor activity of trabectedin","volume":"23","author":"Germano","year":"2013","journal-title":"Cancer Cell"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3344","article-title":"CAF-derived IL6 and GM-CSF cooperate to induce M2-like TAMs\u2013response","volume":"25","author":"Cho","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B93","volume-title":"Estrogen promotes thyroid cancer progression via enhancing infiltration and M2 polarization of tumor-associated macrophage","author":"Seong-yun","year":"2021"},{"key":"B94","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.immuni.2024.11.026","article-title":"Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion","volume":"58","author":"Waibl Polania","year":"2025","journal-title":"Immunity"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.4019","article-title":"Dual immune checkpoint inhibition in patients with aggressive thyroid carcinoma: A phase 2 nonrandomized clinical trial","volume":"10","author":"Sehgal","year":"2024","journal-title":"JAMA Oncol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1016\/j.cell.2018.10.014","article-title":"Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells","volume":"175","author":"Andr\u00e9","year":"2018","journal-title":"Cell"},{"key":"B97","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41392-020-00348-8","article-title":"Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy","volume":"5","author":"Cao","year":"2020","journal-title":"Signal Transduction Targeted Ther"},{"key":"B98","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nri.2017.87","article-title":"The pros and cons of dying tumour cells in adaptive immune responses","volume":"17","author":"Wang","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B99","doi-asserted-by":"publisher","first-page":"e00105","DOI":"10.1136\/jitc-2020-001054","article-title":"Natural killer cells in the human lung tumor microenvironment display immune inhibitory functions","volume":"8","author":"Russick","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2022.2046931","article-title":"Targeting NKG2A to boost anti-tumor CD8 T-cell responses in human colorectal cancer","volume":"11","author":"Ducoin","year":"2022","journal-title":"Oncoimmunology"},{"key":"B101","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1002\/ijc.33859","article-title":"NKG2A is a late immune checkpoint on CD8 T cells and marks repeated stimulation and cell division","volume":"150","author":"Borst","year":"2022","journal-title":"Int J Cancer"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1922-8","article-title":"B cells and tertiary lymphoid structures promote immunotherapy response","volume":"577","author":"Helmink","year":"2020","journal-title":"Nature"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00407","article-title":"Tertiary lymphoid structures in cancers: prognostic value, regulation, and manipulation for therapeutic intervention","volume":"7","author":"Saut\u00e8s-Fridman","year":"2016","journal-title":"Front Immunol"},{"key":"B104","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s00262-025-03952-1","article-title":"Distinct maturity and spatial distribution of tertiary lymphoid structures in head and neck squamous cell carcinoma: implications for tumor immunity and clinical outcomes","volume":"74","author":"Xu","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1111\/imm.70020","article-title":"Tertiary lymphoid structures: allies of cancer immunotherapy","author":"Li","year":"2025","journal-title":"Immunology"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxv034","article-title":"Regulatory B cells in anti-tumor immunity","volume":"27","author":"Zhang","year":"2015","journal-title":"Int Immunol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1038\/nri3857","article-title":"Antibody-independent functions of B cells: a focus on cytokines","volume":"15","author":"Shen","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-074934","article-title":"Immune regulatory function of B cells","volume":"30","author":"Mauri","year":"2012","journal-title":"Annu Rev Immunol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0085-8","article-title":"A natural killer\u2013dendritic cell axis defines checkpoint therapy\u2013responsive tumor microenvironments","volume":"24","author":"Barry","year":"2018","journal-title":"Nat Med"},{"key":"B110","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41577-019-0210-z","article-title":"Dendritic cells in cancer immunology and immunotherapy","volume":"20","author":"Wculek","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03059","article-title":"Dendritic cells and CD8 T cell immunity in tumor microenvironment","volume":"9","author":"Fu","year":"2018","journal-title":"Front Immunol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.03.005","article-title":"Adaptive immunity after cell death","volume":"34","author":"Zelenay","year":"2013","journal-title":"Trends Immunol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.03.012","article-title":"Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition","volume":"44","author":"Salmon","year":"2016","journal-title":"Immunity"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.031","article-title":"Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity","volume":"11","author":"Corrales","year":"2015","journal-title":"Cell Rep"},{"key":"B115","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1097\/01.cji.0000192106.32206.30","article-title":"Mechanism of anticancer host response induced by OK-432, a streptococcal preparation, mediated by phagocytosis and Toll-like receptor 4 signaling","volume":"29","author":"Okamoto","year":"2006","journal-title":"J Immunother"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/nature25501","article-title":"TGF\u03b2 attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells","volume":"554","author":"Mariathasan","year":"2018","journal-title":"Nature"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-16-0169","article-title":"Perspectives for immunotherapy in endocrine cancer","volume":"23","author":"Latteyer","year":"2016","journal-title":"Endocr Relat Cancer"},{"key":"B118","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.ccell.2021.04.014","article-title":"Conserved pan-cancer microenvironment subtypes predict response to immunotherapy","volume":"39","author":"Bagaev","year":"2021","journal-title":"Cancer Cell"},{"key":"B119","doi-asserted-by":"publisher","first-page":"eabf3657","DOI":"10.1126\/sciadv.abf3657","article-title":"Characterizing dedifferentiation of thyroid cancer by integrated analysis","volume":"7","author":"Luo","year":"2021","journal-title":"Sci Adv"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20163934","article-title":"The immune landscape of thyroid cancer in the context of immune checkpoint inhibition","volume":"20","author":"Varricchi","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B121","doi-asserted-by":"publisher","first-page":"e006234","DOI":"10.1136\/jitc-2022-006234","article-title":"Spatial multi-omics revealed the impact of tumor ecosystem heterogeneity on immunotherapy efficacy in patients with advanced non-small cell lung cancer treated with bispecific antibody","volume":"11","author":"Song","year":"2023","journal-title":"J Immunotherapy Cancer"},{"key":"B122","doi-asserted-by":"publisher","first-page":"btaf027","DOI":"10.1093\/bioinformatics\/btaf027","article-title":"Trajectory Inference with Cell\u2013Cell Interactions (TICCI): intercellular communication improves the accuracy of trajectory inference methods","volume":"41","author":"Fu","year":"2025","journal-title":"Bioinformatics"},{"key":"B123","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s41392-022-00962-8","article-title":"Integrating single-cell RNA sequencing with spatial transcriptomics reveals immune landscape for interstitial cystitis","volume":"7","author":"Peng","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-6912640\/v1","article-title":"Single-cell and spatial transcriptomics unveil M-MDSC\u2013tumor crosstalk driving EMT in HCC via THBS1-SDC4 axis","author":"Liu","year":"2025","journal-title":"Research Square"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.7150\/thno.95971","article-title":"Single cell analyses reveal the PD-1 blockade response-related immune features in hepatocellular carcinoma","volume":"14","author":"Li","year":"2024","journal-title":"Theranostics"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000791","article-title":"Epigenetic therapy to enhance therapeutic effects of PD-1 inhibition in therapy-resistant melanoma","volume":"32","author":"Sah","year":"2022","journal-title":"Melanoma Res"},{"key":"B127","doi-asserted-by":"publisher","first-page":"e99988","DOI":"10.1371\/journal.pone.0099988","article-title":"DMXAA causes tumor site-specific vascular disruption in murine non-small cell lung cancer, and like the endogenous non-canonical cyclic dinucleotide STING agonist, 2'3'-cGAMP, induces M2 macrophage repolarization","volume":"9","author":"Downey","year":"2014","journal-title":"PloS One"},{"key":"B128","doi-asserted-by":"publisher","first-page":"20977","DOI":"10.1038\/s41598-024-72020-y","article-title":"New insights into the mechanisms of the extracellular matrix and its therapeutic potential in anaplastic thyroid carcinoma","volume":"14","author":"Xia","year":"2024","journal-title":"Sci Rep"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2022.01.003","article-title":"Immunotherapy in anaplastic thyroid cancer: Case series","volume":"121","author":"Shih","year":"2022","journal-title":"J Formosan Med Assoc"},{"key":"B130","article-title":"Trametinib before surgery for the treatment of BRAF-mutated anaplastic thyroid cancer","author":"Pembrolizumab","year":"2020","journal-title":"ClinicalTrials"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.4729","article-title":"Anti\u2013programmed death ligand 1 plus targeted therapy in anaplastic thyroid carcinoma: a nonrandomized clinical trial","volume":"10","author":"Cabanillas","year":"2024","journal-title":"JAMA Oncol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-3417","article-title":"Combination targeted therapy with pembrolizumab and lenvatinib in progressive, radioiodine-refractory differentiated thyroid cancers","volume":"30","author":"French","year":"2024","journal-title":"Clin Cancer Res"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-023-14031-z","article-title":"The efficacy and safety of surufatinib combined with anti PD-1 antibody toripalimab in neoadjuvant treatment of locally advanced differentiated thyroid cancer: a phase II study","volume":"30","author":"Chen","year":"2023","journal-title":"Ann Surg Oncol"},{"key":"B134","doi-asserted-by":"publisher","first-page":"12765","DOI":"10.1038\/s41598-023-39503-w","article-title":"Changes in peripheral blood immune cell population in thyroid cancer patients treated with lenvatinib","volume":"13","author":"Jin","year":"2023","journal-title":"Sci Rep"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0322","article-title":"Combination of lenvatinib and pembrolizumab is an effective treatment option for anaplastic and poorly differentiated thyroid carcinoma","volume":"31","author":"Dierks","year":"2021","journal-title":"Thyroid"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.12.014","article-title":"Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study","volume":"33","author":"Subbiah","year":"2022","journal-title":"Ann Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1738583\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T06:38:35Z","timestamp":1767595115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1738583\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":136,"alternative-id":["10.3389\/fimmu.2025.1738583"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1738583","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]},"article-number":"1738583"}}