{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:59:21Z","timestamp":1791665961829,"version":"4.3.4"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Behring Foundation","award":["25000.029124\/2021-31"],"award-info":[{"award-number":["25000.029124\/2021-31"]}]},{"name":"CNRS IIPACT International Research Network"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy where endogenous steroid excess may foster immune evasion. However, whether this hormonal axis directly modulates the antigen presentation machinery remains unclear. Methods: We applied an immunoinformatics approach to the TCGA-ACC cohort (n = 79) to investigate relationships among steroid phenotype, HLA expression, tumor microenvironment (TME), and patient outcome. Key findings were assessed in an independent validation cohort (ENSAT-ACC, n = 44) using C1A\/C1B molecular subtypes corresponding to the steroid phenotypes. Results: Stratification by steroid phenotype revealed two distinct immunological profiles. The high steroid production (HSP) phenotype was associated with suppressed HLA expression and a lymphocyte-depleted \u201ccold\u201d TME. In contrast, the low steroid production (LSP) phenotype displayed elevated HLA expression, enriched T-cell infiltration, and upregulation of immune checkpoints (e.g., PDCD1, CTLA4), consistent with an inflamed but exhausted TME. The core signature of HLA downregulation in the HSP-like phenotype (C1A) and the significant survival advantage of the LSP-like phenotype (C1B) were confirmed in the validation cohort, demonstrating biological robustness despite platform and sample size differences. Conclusions: These findings identify the steroid phenotype as a critical regulator of immune escape in ACC. Our results support incorporating this stratification as a biomarker for patient selection, identifying LSP tumors as the subgroup most likely to benefit from immune checkpoint blockade due to their \u201chot\u201d yet exhausted microenvironment.<\/jats:p>","DOI":"10.3390\/cancers18020229","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:25:23Z","timestamp":1768213523000},"page":"229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Steroid Phenotype Stratification Reveals Distinct HLA Expression Signatures in Adrenocortical Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2397-4858","authenticated-orcid":false,"given":"Igor S.","family":"Giner","sequence":"first","affiliation":[{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Oncology Division, Curitiba 80250-060, PR, Brazil"},{"name":"Faculdades Pequeno Pr\u00edncipe, Pel\u00e9 Pequeno Pr\u00edncipe Research Hospital, Oncology Laboratory, Av. Igua\u00e7u, 333-Rebou\u00e7as, Curitiba 80230-020, PR, Brazil"},{"name":"Bioinformatics and Systems Biology Laboratory, Federal University of Paran\u00e1, Curitiba 81520-260, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean S. S.","family":"Resende","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Oncology Division, Curitiba 80250-060, PR, Brazil"},{"name":"Faculdades Pequeno Pr\u00edncipe, Pel\u00e9 Pequeno Pr\u00edncipe Research Hospital, Oncology Laboratory, Av. Igua\u00e7u, 333-Rebou\u00e7as, Curitiba 80230-020, PR, Brazil"},{"name":"Bioinformatics and Systems Biology Laboratory, Federal University of Paran\u00e1, Curitiba 81520-260, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o C. D.","family":"Muzzi","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Oncology Division, Curitiba 80250-060, PR, Brazil"},{"name":"Faculdades Pequeno Pr\u00edncipe, Pel\u00e9 Pequeno Pr\u00edncipe Research Hospital, Oncology Laboratory, Av. Igua\u00e7u, 333-Rebou\u00e7as, Curitiba 80230-020, PR, Brazil"},{"name":"Bioinformatics and Systems Biology Laboratory, Federal University of Paran\u00e1, Curitiba 81520-260, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9526-6781","authenticated-orcid":false,"given":"Jos\u00e9 A. M.","family":"Barbuto","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, SP, Brazil"},{"name":"Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology, Hospital das Cl\u00ednicas HCFMUSP, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0584-5681","authenticated-orcid":false,"given":"Enzo","family":"Lalli","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie Mol\u00e9culaire et Cellulaire CNRS UMR7275, Inserm U1323, Universit\u00e9 C\u00f4te d\u2019Azur, 06560 Valbonne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-8131","authenticated-orcid":false,"given":"Mauro A. A.","family":"Castro","sequence":"additional","affiliation":[{"name":"Bioinformatics and Systems Biology Laboratory, Federal University of Paran\u00e1, Curitiba 81520-260, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-2056","authenticated-orcid":false,"given":"Bonald C.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Oncology Division, Curitiba 80250-060, PR, Brazil"},{"name":"Faculdades Pequeno Pr\u00edncipe, Pel\u00e9 Pequeno Pr\u00edncipe Research Hospital, Oncology Laboratory, Av. Igua\u00e7u, 333-Rebou\u00e7as, Curitiba 80230-020, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","first-page":"100759","article-title":"Adrenocortical Carcinoma: Diagnosis, Prognostic Classification and Treatment of Localized and Advanced Disease","volume":"37","author":"Huillard","year":"2023","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-18-0608","article-title":"European Society of Endocrinology Clinical Practice Guidelines on the Management of Adrenocortical Carcinoma in Adults, in Collaboration with the European Network for the Study of Adrenal Tumors","volume":"179","author":"Fassnacht","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lib\u00e9, R. (2015). Adrenocortical Carcinoma (ACC): Diagnosis, Prognosis, and Treatment. Front. Cell Dev. Biol., 3.","DOI":"10.3389\/fcell.2015.00045"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bedrose, S., Daher, M., Altameemi, L., and Habra, M.A. (2020). Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions. Cancers, 12.","DOI":"10.3390\/cancers12020508"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1093\/annonc\/mdv329","article-title":"Prognostic Factors in Stage III\u2013IV Adrenocortical Carcinomas (ACC): An European Network for the Study of Adrenal Tumor (ENSAT) Study","volume":"26","author":"Borget","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17588359211038409","DOI":"10.1177\/17588359211038409","article-title":"Management of Adrenocortical Carcinoma: Are We Making Progress?","volume":"13","author":"Kiesewetter","year":"2021","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"636","DOI":"10.14740\/jocmr3503w","article-title":"The Characteristics and Trends in Adrenocortical Carcinoma: A United States Population Based Study","volume":"10","author":"Sharma","year":"2018","journal-title":"J. Clin. Med. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ccell.2016.04.002","article-title":"Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma","volume":"29","author":"Zheng","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Suzuki, S., Minamidate, T., Shiga, A., Ruike, Y., Ishiwata, K., Naito, K., Ishida, A., Deguchi, H., Fujimoto, M., and Koide, H. (2020). Steroid Metabolites for Diagnosing and Predicting Clinicopathological Features in Cortisol-Producing Adrenocortical Carcinoma. BMC Endocr. Disord., 20.","DOI":"10.1186\/s12902-020-00652-y"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1373\/clinchem.2017.277624","article-title":"A 13-Steroid Serum Panel Based on LC-MS\/MS: Use in Detection of Adrenocortical Carcinoma","volume":"63","author":"Taylor","year":"2017","journal-title":"Clin. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sigala, S., Bothou, C., Penton, D., Abate, A., Peitzsch, M., Cosentini, D., Tiberio, G.A.M., Bornstein, S.R., Berruti, A., and Hantel, C. (2022). A Comprehensive Investigation of Steroidogenic Signaling in Classical and New Experimental Cell Models of Adrenocortical Carcinoma. Cells, 11.","DOI":"10.3390\/cells11091439"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Muzzi, J.C.D., Magno, J.M., Cardoso, M.A., de Moura, J., Castro, M.A.A., and Figueiredo, B.C. (2021). Adrenocortical Carcinoma Steroid Profiles: In Silico Pan-Cancer Analysis of TCGA Data Uncovers Immunotherapy Targets for Potential Improved Outcomes. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.672319"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S1357-4310(99)01451-3","article-title":"HLA Class I Antigen Downregulation in Human Cancers: T-Cell Immunotherapy Revives an Old Story","volume":"5","author":"Hicklin","year":"1999","journal-title":"Mol. Med. Today"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1007\/s00262-010-0893-2","article-title":"The Escape of Cancer from T Lymphocytes: Immunoselection of MHC Class I Loss Variants Harboring Structural-Irreversible \u201cHard\u201d Lesions","volume":"59","author":"Garrido","year":"2010","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.3324\/haematol.2017.184192","article-title":"Hide or Defend, the Two Strategies of Lymphoma Immune Evasion: Potential Implications for Immunotherapy","volume":"103","author":"Houot","year":"2018","journal-title":"Haematologica"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nri.2017.1","article-title":"Immune Regulation by Glucocorticoids","volume":"17","author":"Cain","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10061","DOI":"10.1111\/jcmm.16936","article-title":"Integrative Computational Immunogenomic Profiling of Cortisol-Secreting Adrenocortical Carcinoma","volume":"25","author":"Baechle","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106462","DOI":"10.1016\/j.jsbmb.2024.106462","article-title":"Histopathological Analysis of Tumor Microenvironment in Adrenocortical Carcinoma: Possible Effects of in Situ Disorganized Glucocorticoid Production on Tumor Immunity","volume":"238","author":"Ishikawa","year":"2024","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6072863","DOI":"10.1155\/2019\/6072863","article-title":"Molecular Drivers of Potential Immunotherapy Failure in Adrenocortical Carcinoma","volume":"2019","author":"Fiorentini","year":"2019","journal-title":"J. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/s41416-021-01400-2","article-title":"Pan-Cancer Association of HLA Gene Expression with Cancer Prognosis and Immunotherapy Efficacy","volume":"125","author":"Schaafsma","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/ng.2953","article-title":"Integrated Genomic Characterization of Adrenocortical Carcinoma","volume":"46","author":"Fassnacht","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41587-020-0546-8","article-title":"Visualizing and Interpreting Cancer Genomics Data via the Xena Platform","volume":"38","author":"Goldman","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2018.03.022","article-title":"Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer","volume":"173","author":"Hoadley","year":"2018","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/ejendo\/lvaf129","article-title":"Unexpected Discrepancies between Steroid Intra-Tissular Content in Adrenal Tumors and Clinical Diagnosis of Steroid Excess","volume":"193","author":"Thomeret","year":"2025","journal-title":"Eur. J. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","article-title":"The Immune Landscape of Cancer","volume":"48","author":"Thorsson","year":"2018","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Guan, Y., Yue, S., Chen, Y., Pan, Y., An, L., Du, H., and Liang, C. (2022). Molecular Cluster Mining of Adrenocortical Carcinoma via Multi-Omics Data Analysis Aids Precise Clinical Therapy. Cells, 11.","DOI":"10.3390\/cells11233784"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lu, Q., Nie, R., Luo, J., Wang, X., and You, L. (2023). Identifying Immune-Specific Subtypes of Adrenocortical Carcinoma Based on Immunogenomic Profiling. Biomolecules, 13.","DOI":"10.3390\/biom13010104"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103617","DOI":"10.1016\/j.esmoop.2024.103617","article-title":"Comprehensive Genomic Analysis of Adrenocortical Carcinoma Reveals Genetic Profiles Associated with Patient Survival","volume":"9","author":"Juhlin","year":"2024","journal-title":"ESMO Open"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: A Bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Muzzi, J.C.D., Magno, J.M., Souza, J.S., Alvarenga, L.M., de Moura, J.F., Figueiredo, B.C., and Castro, M.A.A. (2022). Comprehensive Characterization of the Regulatory Landscape of Adrenocortical Carcinoma: Novel Transcription Factors and Targets Associated with Prognosis. Cancers, 14.","DOI":"10.3390\/cancers14215279"},{"key":"ref_31","unstructured":"Kolde, R. (2025, June 30). Pheatmap: Pretty Heatmaps. R Package Version 1.0.12. Available online: https:\/\/CRAN.R-project.org\/package=pheatmap."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex Heatmaps Reveal Patterns and Correlations in Multidimensional Genomic Data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","article-title":"Estimating the Population Abundance of Tissue-Infiltrating Immune and Stromal Cell Populations Using Gene Expression","volume":"17","author":"Becht","year":"2016","journal-title":"Genome Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zeng, D., Ye, Z., Shen, R., Yu, G., Wu, J., Xiong, Y., Zhou, R., Qiu, W., Huang, N., and Sun, L. (2021). IOBR: Multi-Omics Immuno-Oncology Biological Research to Decode Tumor Microenvironment and Signatures. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.687975"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.immuni.2020.08.005","article-title":"Endogenous Glucocorticoid Signaling Regulates CD8+ T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment","volume":"53","author":"Acharya","year":"2020","journal-title":"Immunity"},{"key":"ref_36","unstructured":"Wei, T., Simko, V., Levy, M., Xie, Y., Jin, Y., Zemla, J., Freidank, M., Cai, J., and Protivinsky, T. (2025, August 01). Corrplot: Visualization of a Correlation Matrix 2024. Available online: https:\/\/cran.r-project.org\/web\/packages\/corrplot\/corrplot.pdf."},{"key":"ref_37","unstructured":"Therneau, T.M. (2025, August 04). A Package for Survival Analysis in R. R Package Version 3.8-3. Available online: https:\/\/CRAN.R-project.org\/package=survival."},{"key":"ref_38","unstructured":"Kassambara, A., Kosinski, M., and Biecek, P. (2025, August 04). Survminer: Drawing Survival Curves Using \u2018ggplot2\u2019. R Package Version 0.5.0. Available online: https:\/\/CRAN.R-project.org\/package=survminer."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2307\/3001968","article-title":"Individual Comparisons by Ranking Methods","volume":"1","author":"Wilcoxon","year":"1945","journal-title":"Biom. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1214\/aoms\/1177730491","article-title":"On a Test of Whether One of Two Random Variables Is Stochastically Larger than the Other","volume":"18","author":"Mann","year":"1947","journal-title":"Ann. Math. Stat."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kotz, S., and Johnson, N.L. (1992). Statistical Methods for Research Workers. Breakthroughs in Statistics: Methodology and Distribution, Springer.","DOI":"10.1007\/978-1-4612-4380-9"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"R. Stat. Soc. J. Ser. B Methodol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1200\/JCO.2008.18.5678","article-title":"Gene Expression Profiling Reveals a New Classification of Adrenocortical Tumors and Identifies Molecular Predictors of Malignancy and Survival","volume":"27","author":"Rickman","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1002\/pbc.25118","article-title":"Low Expression of HLA-DRA, HLA-DPA1, and HLA-DPB1 Is Associated with Poor Prognosis in Pediatric Adrenocortical Tumors (ACT)","volume":"61","author":"Leite","year":"2014","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1158\/0008-5472.CAN-06-3767","article-title":"Gene Expression Profiling of Childhood Adrenocortical Tumors","volume":"67","author":"West","year":"2007","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6247","DOI":"10.1158\/1078-0432.CCR-15-2738","article-title":"Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children\u2019s Oncology Group Study","volume":"22","author":"Pinto","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s40164-024-00543-1","article-title":"Tumor Battlefield within Inflamed, Excluded or Desert Immune Phenotypes: The Mechanisms and Strategies","volume":"13","author":"Zheng","year":"2024","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1158\/1078-0432.CCR-18-4085","article-title":"The Immune Subtypes and Landscape of Squamous Cell Carcinoma","volume":"25","author":"Li","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41392-024-01979-x","article-title":"Cold and Hot Tumors: From Molecular Mechanisms to Targeted Therapy","volume":"9","author":"Wu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1126\/science.270.5234.286","article-title":"Immunosuppression by Glucocorticoids: Inhibition of NF-\u03baB Activity Through Induction of I\u03baB Synthesis","volume":"270","author":"Auphan","year":"1995","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1164\/ajrccm\/154.2_Pt_2.S11","article-title":"Molecular Mechanisms of Immunosuppression and Anti-Inflammatory Activities by Glucocorticoids","volume":"154","author":"Didonato","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7041","DOI":"10.1038\/s41467-021-27349-7","article-title":"Glucocorticoid Receptor Regulates PD-L1 and MHC-I in Pancreatic Cancer Cells to Promote Immune Evasion and Immunotherapy Resistance","volume":"12","author":"Deng","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.aar4060","article-title":"Cancer Immunotherapy Using Checkpoint Blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1210\/clinem\/dgae109","article-title":"Expression and Prognostic Relevance of PD-1, PD-L1, and CTLA-4 Immune Checkpoints in Adrenocortical Carcinoma","volume":"109","author":"Landwehr","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1158\/2326-6066.CIR-18-0277","article-title":"T Cell\u2013Inflamed versus Non-T Cell\u2013Inflamed Tumors: A Conceptual Framework for Cancer Immunotherapy Drug Development and Combination Therapy Selection","volume":"6","author":"Trujillo","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s40425-018-0479-7","article-title":"High and Low Mutational Burden Tumors versus Immunologically Hot and Cold Tumors and Response to Immune Checkpoint Inhibitors","volume":"6","author":"Vareki","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e48009","DOI":"10.2196\/48009","article-title":"Ethical Considerations of Using ChatGPT in Health Care","volume":"25","author":"Wang","year":"2023","journal-title":"J. Med. Internet Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1210\/jc.2005-2730","article-title":"Clinical and Biological Features in the Prognosis of Adrenocortical Cancer: Poor Outcome of Cortisol-Secreting Tumors in a Series of 202 Consecutive Patients","volume":"91","author":"Abiven","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1530\/EJE-18-0450","article-title":"Influence of Hormonal Functional Status on Survival in Adrenocortical Carcinoma: Systematic Review and Meta-Analysis","volume":"179","author":"Vanbrabant","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.mce.2011.09.040","article-title":"Differences in the Molecular Mechanisms of Adrenocortical Tumorigenesis between Children and Adults","volume":"351","author":"Faria","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e000469","DOI":"10.1136\/jitc-2019-000469","article-title":"Interplay between Glucocorticoids and Tumor-Infiltrating Lymphocytes on the Prognosis of Adrenocortical Carcinoma","volume":"8","author":"Landwehr","year":"2020","journal-title":"J. Immunother. Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/2\/229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:46:39Z","timestamp":1768214799000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/2\/229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":61,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["cancers18020229"],"URL":"https:\/\/doi.org\/10.3390\/cancers18020229","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]}}}