{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:16:20Z","timestamp":1788441380454,"version":"build-2803163510"},"reference-count":34,"publisher":"IMR Press","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011789","name":"Jilin Provincial Department of Science and Technology","doi-asserted-by":"crossref","award":["YDZJ202201ZYTS168"],"award-info":[{"award-number":["YDZJ202201ZYTS168"]}],"id":[{"id":"10.13039\/501100011789","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010097","name":"China Association for Science and Technology","doi-asserted-by":"crossref","award":["QT202218"],"award-info":[{"award-number":["QT202218"]}],"id":[{"id":"10.13039\/100010097","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82103343"],"award-info":[{"award-number":["82103343"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Small cell lung carcinoma (SCLC) is a highly aggressive, rapidly proliferating malignancy largely corresponding to immune-cold tumor type. The role of the key oncogene c-Myc in regulating the complex immune microenvironment of SCLC remains unknown.Methods:Immunohistochemistry and multiplex immunofluorescence techniques were used to analyze c-Myc expression and immune cell infiltration. c-Myc and \u03b2-catenin expression were analyzed using western blotting. Flow cytometry was used to quantify the expression of immunosuppressive ligands\u2014including programmed death ligand 1 (PD-L1), CD47, CD155, and human leukocyte antigen-E (HLA-E)\u2014and characterize the function of T cells and macrophages. Cytokine levels were evaluated using enzyme-linked immunosorbent assays.Results:c-Myc expression in high tumor-infiltrating lymphocyte infiltration (TILhigh) tumor exceeded that in TILlow tumors (n = 24) and was positively correlated with CD163+ macrophage infiltration (p = 0.0180). Immunosuppressive ligands were universally expressed on SCLC cells. 10058-F4\u2014a c-Myc inhibitor\u2014substantially downregulated the expression of PD-L1, CD47, and CD155 and upregulated HLA-E expression. In the coculture system, the inhibition of c-Myc in SCLC cells significantly upregulated interferon-gamma production in Jurkat cells, inhibited macrophage phagocytosis, and decreased cytokine concentrations in the supernatant. Further mechanistic studies revealed that c-Myc inhibition modulated the Notch signaling pathway and reduced the expression of E-cadherin, vascular endothelial (VE)-cadherin, and \u03b2-catenin. A \u03b2-catenin agonist improved the regulatory effect of 10058-F4 on the immunosuppressive ligands in SCLC cells.Conclusions:c-Myc expression in SCLC is associated with immune infiltration and may regulate the expression of immune-related ligands on SCLC cells via WNT\/\u03b2-catenin signaling.<\/jats:p>","DOI":"10.31083\/fbl52899","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:35:31Z","timestamp":1788438931000},"source":"Crossref","is-referenced-by-count":0,"title":["Association of c-Myc and Immune Cell Infiltration in Small Cell Lung Carcinoma"],"prefix":"10.31083","volume":"31","author":[{"given":"Peiyan","family":"Zhao","sequence":"first","affiliation":[{"name":"Translational Oncology Research Lab, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"},{"name":"Jilin Provincial Key Laboratory of Molecular Diagnostics for Malignant Tumor, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Lab, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"},{"name":"Jilin Provincial Key Laboratory of Molecular Diagnostics for Malignant Tumor, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Lab, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"},{"name":"Jilin Provincial Key Laboratory of Molecular Diagnostics for Malignant Tumor, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Di","sequence":"additional","affiliation":[{"name":"Biobank, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Lab, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"},{"name":"Jilin Provincial Key Laboratory of Molecular Diagnostics for Malignant Tumor, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tian","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Lab, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"},{"name":"Jilin Provincial Key Laboratory of Molecular Diagnostics for Malignant Tumor, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhong","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Lab, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"},{"name":"Jilin Provincial Key Laboratory of Molecular Diagnostics for Malignant Tumor, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlin","family":"Liang","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Lab, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"},{"name":"Jilin Provincial Key Laboratory of Molecular Diagnostics for Malignant Tumor, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6636-9017","authenticated-orcid":true,"given":"Haifeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Translational Oncology Research Lab, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"},{"name":"Jilin Provincial Key Laboratory of Molecular Diagnostics for Malignant Tumor, Jilin Cancer Hospital, 130000 Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Filho AM, Laversanne M, Ferlay J, Colombet M, Pi\u00f1eros M, Znaor A, et al. The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide. International Journal of Cancer. 2025; 156: 1336\u20131346.","DOI":"10.1002\/ijc.35278"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Fr\u00fch M, De Ruysscher D, Popat S, Crin\u00f2 L, Peters S, Felip E, et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology: Official Journal of the European Society for Medical Oncology. 2013; 24: vi99\u2013vi105.","DOI":"10.1093\/annonc\/mdt178"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nature Reviews. Cancer. 2017; 17: 725\u2013737.","DOI":"10.1038\/nrc.2017.87"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Sen T, Takahashi N, Chakraborty S, Takebe N, Nassar AH, Karim NA, et al. Emerging advances in defining the molecular and therapeutic landscape of small-cell lung cancer. Nature Reviews. Clinical Oncology. 2024; 21: 610\u2013627.","DOI":"10.1038\/s41571-024-00914-x"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Sabari JK, Lok BH, Laird JH, Poirier JT, Rudin CM. Unravelling the biology of SCLC: implications for therapy. Nature Reviews. Clinical Oncology. 2017; 14: 549\u2013561.","DOI":"10.1038\/nrclinonc.2017.71"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2021; 39: 619\u2013630.","DOI":"10.1200\/JCO.20.01055"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet (London, England). 2019; 394: 1929\u20131939.","DOI":"10.1016\/S0140-6736(19)32222-6"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Das SK, Lewis BA, Levens D. MYC: a complex problem. Trends in Cell Biology. 2023; 33: 235\u2013246.","DOI":"10.1016\/j.tcb.2022.07.006"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Casey SC, Baylot V, Felsher DW. The MYC oncogene is a global regulator of the immune response. Blood. 2018; 131: 2007\u20132015.","DOI":"10.1182\/blood-2017-11-742577"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Ireland AS, Micinski AM, Kastner DW, Guo B, Wait SJ, Spainhower KB, et al. MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate. Cancer Cell. 2020; 38: 60\u201378.e12.","DOI":"10.1016\/j.ccell.2020.05.001"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Kanemura H, Hayashi H, Tomida S, Tanizaki J, Suzuki S, Kawanaka Y, et al. The Tumor Immune Microenvironment and Frameshift Neoantigen Load Determine Response to PD-L1 Blockade in Extensive-Stage SCLC. JTO Clinical and Research Reports. 2022; 3: 100373.","DOI":"10.1016\/j.jtocrr.2022.100373"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Alburquerque-Bejar JJ, Navajas-Chocarro P, Saigi M, Ferrero-Andres A, Morillas JM, Vilarrubi A, et al. MYC activation impairs cell-intrinsic IFN\u03b3 signaling and confers resistance to anti-PD1\/PD-L1 therapy in lung cancer. Cell Reports. Medicine. 2023; 4: 101006.","DOI":"10.1016\/j.xcrm.2023.101006"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Zhao P, Sun X, Li H, Liu Y, Cui Y, Tian L, et al. c-Myc Targets HDAC3 to Suppress NKG2DL Expression and Innate Immune Response in N-Type SCLC through Histone Deacetylation. Cancers. 2022; 14: 457.","DOI":"10.3390\/cancers14030457"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Tian L, Li H, Zhao P, Liu Y, Lu Y, Zhong R, et al. C-Myc-induced hypersialylation of small cell lung cancer facilitates pro-tumoral phenotypes of macrophages. IScience. 2023; 26: 107771.","DOI":"10.1016\/j.isci.2023.107771"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Liu JX, Lu T, Xia Y, Yang J, Jiang YF, Zhao Y, et al. Expression and correlation of Surfeit 4 gene in esophageal squamous cell carcinoma. Holistic Integrative Oncology. 2024; 3: 66.","DOI":"10.1007\/s44178-024-00141-5"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. The Lancet. Oncology. 2018; 19: 40\u201350.","DOI":"10.1016\/S1470-2045(17)30904-X"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, et al. Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nature Reviews. Cancer. 2019; 19: 289\u2013297.","DOI":"10.1038\/s41568-019-0133-9"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Gay CM, Stewart CA, Park EM, Diao L, Groves SM, Heeke S, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021; 39: 346\u2013360.e7.","DOI":"10.1016\/j.ccell.2020.12.014"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Russo GC, Crawford AJ, Clark D, Cui J, Carney R, Karl MN, et al. E-cadherin interacts with EGFR resulting in hyper-activation of ERK in multiple models of breast cancer. Oncogene. 2024; 43: 1445\u20131462.","DOI":"10.1038\/s41388-024-03007-2"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Ye YC, Zhao JL, Lu YT, Gao CC, Yang Y, Liang SQ, et al. NOTCH Signaling via WNT Regulates the Proliferation of Alternative, CCR2-Independent Tumor-Associated Macrophages in Hepatocellular Carcinoma. Cancer Research. 2019; 79: 4160\u20134172.","DOI":"10.1158\/0008-5472.CAN-18-1691"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Busch SE, Hanke ML, Kargl J, Metz HE, MacPherson D, Houghton AM. Lung Cancer Subtypes Generate Unique Immune Responses. Journal of Immunology (Baltimore, Md.: 1950). 2016; 197: 4493\u20134503.","DOI":"10.4049\/jimmunol.1600576"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Chan JM, Quintanal-Villalonga \u00c1, Gao VR, Xie Y, Allaj V, Chaudhary O, et al. Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer. Cancer Cell. 2021; 39: 1479\u20131496.e18.","DOI":"10.1016\/j.ccell.2021.09.008"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Nirala BK, Yustein JT. The Role of MYC in Tumor Immune Microenvironment Regulation: Insights and Future Directions. Frontiers in Bioscience (Landmark Edition). 2025; 30: 37304.","DOI":"10.31083\/FBL37304"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Chen Y, Anwar M, Wang X, Zhang B, Ma B. Integrative transcriptomic and single-cell analysis reveals IL27RA as a key immune regulator and therapeutic indicator in breast cancer. Discover Oncology. 2025; 16: 977.","DOI":"10.1007\/s12672-025-02811-w"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Li K, Zeng X, Zhang Z, Wang K, Pan Y, Wu Z, et al. Pan-immune-inflammatory values predict survival in patients after radical surgery for non-metastatic colorectal cancer: A retrospective study. Oncology Letters. 2025; 29: 197.","DOI":"10.3892\/ol.2025.14943"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Cassetta L, Pollard JW. Tumor-associated macrophages. Current Biology: CB. 2020; 30: R246\u2013R248.","DOI":"10.1016\/j.cub.2020.01.031"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"van Duijn A, Van der Burg SH, Scheeren FA. CD47\/SIRP\u03b1 axis: bridging innate and adaptive immunity. Journal for Immunotherapy of Cancer. 2022; 10: e004589.","DOI":"10.1136\/jitc-2022-004589"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Zhang S, Rautela J, Bediaga NG, Kolesnik TB, You Y, Nie J, et al. CIS controls the functional polarization of GM-CSF-derived macrophages. Cellular & Molecular Immunology. 2023; 20: 65\u201379.","DOI":"10.1038\/s41423-022-00957-z"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Qu S, Fetsch P, Thomas A, Pommier Y, Schrump DS, Miettinen MM, et al. Molecular Subtypes of Primary SCLC Tumors and Their Associations With Neuroendocrine and Therapeutic Markers. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer. 2022; 17: 141\u2013153.","DOI":"10.1016\/j.jtho.2021.08.763"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Sen T, Rodriguez BL, Chen L, Corte CMD, Morikawa N, Fujimoto J, et al. Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer. Cancer Discovery. 2019; 9: 646\u2013661.","DOI":"10.1158\/2159-8290.CD-18-1020"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Solta A, Ernhofer B, Boettiger K, Megyesfalvi Z, Heeke S, Hoda MA, et al. Small cells - big issues: biological implications and preclinical advancements in small cell lung cancer. Molecular Cancer. 2024; 23: 41.","DOI":"10.1186\/s12943-024-01953-9"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Tenjin Y, Matsuura K, Kudoh S, Usuki S, Yamada T, Matsuo A, et al. Distinct transcriptional programs of SOX2 in different types of small cell lung cancers. Laboratory Investigation; a Journal of Technical Methods and Pathology. 2020; 100: 1575\u20131588.","DOI":"10.1038\/s41374-020-00479-0"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Cheng Y, Spigel DR, Cho BC, Laktionov KK, Fang J, Chen Y, et al. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. The New England Journal of Medicine. 2024; 391: 1313\u20131327.","DOI":"10.1056\/NEJMoa2404873"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Chen Y, Zhang B, Wang X, Chen Y, Anwar M, Fan J, et al. Prognostic value of preoperative modified Glasgow prognostic score in predicting overall survival in breast cancer patients: A retrospective cohort study. Oncology Letters. 2025; 29: 180.","DOI":"10.3892\/ol.2025.14926"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/8\/10.31083\/FBL52899","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:36:42Z","timestamp":1788439002000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/8\/10.31083\/FBL52899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026]]}},"alternative-id":["S2768-6701(26)02190-8"],"URL":"https:\/\/doi.org\/10.31083\/fbl52899","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]},"article-number":"52899"}}