{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:30:47Z","timestamp":1787139047152,"version":"build-2736575974"},"reference-count":159,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Innovations in cancer immunotherapy have resulted in the development of several novel immunotherapeutic strategies that can disrupt immunosuppression. One key advancement lies in immune checkpoint inhibitors (ICIs), which have shown significant clinical efficacy and increased survival rates in patients with various therapy-resistant cancers. This immune intervention consists of monoclonal antibodies directed against inhibitory receptors (e.g., PD-1) on cytotoxic CD8 T cells or against corresponding ligands (e.g., PD-L1\/PD-L2) overexpressed on cancer cells and other cells in the tumor microenvironment (TME). However, not all cancer cells respond\u2014there are still poor clinical responses, immune-related adverse effects, adaptive resistance, and vulnerability to ICIs in a subset of patients with cancer. This challenge showcases the heterogeneity of cancer, emphasizing the existence of additional immunoregulatory mechanisms in many patients. Therefore, it is essential to investigate PD-L1\u2019s interaction with other oncogenic genes and pathways to further advance targeted therapies and address resistance mechanisms. Accordingly, our aim was to investigate the mechanisms governing PD-L1 expression in tumor cells, given its correlation with immune evasion, to uncover novel mechanisms for decreasing PD-L1 expression and restoring anti-tumor immune responses. Numerous studies have demonstrated that the upregulation of Raf Kinase Inhibitor Protein (RKIP) in many cancers contributes to the suppression of key hyperactive pathways observed in malignant cells, alongside its broadening involvement in immune responses and the modulation of the TME. We, therefore, hypothesized that the role of PD-L1 in cancer immune surveillance may be inversely correlated with the low expression level of the tumor suppressor Raf Kinase Inhibitor Protein (RKIP) expression in cancer cells. This hypothesis was investigated and we found several signaling cross-talk pathways between the regulations of both RKIP and PD-L1 expressions. These pathways and regulatory factors include the MAPK and JAK\/STAT pathways, GSK3\u03b2, cytokines IFN-\u03b3 and IL-1\u03b2, Sox2, and transcription factors YY1 and NF\u03baB. The pathways that upregulated PD-L1 were inhibitory for RKIP expression and vice versa. Bioinformatic analyses in various human cancers demonstrated the inverse relationship between PD-L1 and RKIP expressions and their prognostic roles. Therefore, we suspect that the direct upregulation of RKIP and\/or the use of targeted RKIP inducers in combination with ICIs could result in a more targeted anti-tumor immune response\u2014addressing the therapeutic challenges related to PD-1\/PD-L1 monotherapy alone.<\/jats:p>","DOI":"10.3390\/cells13100864","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T09:10:22Z","timestamp":1715937022000},"page":"864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cross-Talks between Raf Kinase Inhibitor Protein and Programmed Cell Death Ligand 1 Expressions in Cancer: Role in Immune Evasion and Therapeutic Implications"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9693-6730","authenticated-orcid":false,"given":"Mai","family":"Ho","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bonavida","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, Jonsson Comprehensive Cancer, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"150923","DOI":"10.1016\/j.soncn.2019.08.002","article-title":"Cancer and the Immune System: The History and Background of Immunotherapy","volume":"35","author":"Abbott","year":"2019","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"670","DOI":"10.6004\/jnccn.2015.0199","article-title":"Principles of Immunotherapy","volume":"13","author":"Olszanski","year":"2015","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-032414-112043","article-title":"Innate Immune Recognition of Cancer","volume":"33","author":"Woo","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e001111","DOI":"10.1136\/jitc-2020-001111","article-title":"Antigen Processing and Presentation in Cancer Immunotherapy","volume":"8","author":"Lee","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev-immunol-031210-101324","article-title":"Natural Innate and Adaptive Immunity to Cancer","volume":"29","author":"Vesely","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chen, Y., Song, Y., Du, W., Gong, L., Chang, H., and Zou, Z. (2019). Tumor-Associated Macrophages: An Accomplice in Solid Tumor Progression. J. Biomed. Sci., 26.","DOI":"10.1186\/s12929-019-0568-z"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1133308","DOI":"10.3389\/fimmu.2023.1133308","article-title":"Tumor Microenvironment-Mediated Immune Evasion in Hepatocellular Carcinoma","volume":"14","author":"Chen","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1093\/annonc\/mdw168","article-title":"Targeting the Tumor Microenvironment: Removing Obstruction to Anticancer Immune Responses and Immunotherapy","volume":"27","author":"Pitt","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14733","DOI":"10.1073\/pnas.1009731107","article-title":"Cooperation of Tim-3 and PD-1 in CD8 T-Cell Exhaustion during Chronic Viral Infection","volume":"107","author":"Jin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41416-020-01048-4","article-title":"Cytotoxic CD8+ T Cells in Cancer and Cancer Immunotherapy","volume":"124","author":"Raskov","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yin, Z., Zhang, Y., and Wang, X. (2021). Advances in Chimeric Antigen Receptor T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Biomark. Res., 9.","DOI":"10.1186\/s40364-021-00309-5"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12943-023-01723-z","article-title":"CAR-Cell Therapy in the Era of Solid Tumor Treatment: Current Challenges and Emerging Therapeutic Advances","volume":"22","author":"Maalej","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1080\/14712598.2022.2064711","article-title":"Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy: Recent Advances, Challenges, and Future Directions","volume":"22","author":"Presti","year":"2022","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00281-018-0703-z","article-title":"Principles of Adoptive T Cell Therapy in Cancer","volume":"41","author":"Met","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"328rv4","DOI":"10.1126\/scitranslmed.aad7118","article-title":"PD-L1 (B7-H1) and PD-1 Pathway Blockade for Cancer Therapy: Mechanisms, Response Biomarkers, and Combinations","volume":"8","author":"Zou","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2017-06-741033","article-title":"CTLA-4: A Moving Target in Immunotherapy","volume":"131","author":"Rowshanravan","year":"2018","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12943-018-0928-4","article-title":"Role of the Tumor Microenvironment in PD-L1\/PD-1-Mediated Tumor Immune Escape","volume":"18","author":"Jiang","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/intimm\/dxm057","article-title":"PD-1 and PD-1 Ligands: From Discovery to Clinical Application","volume":"19","author":"Okazaki","year":"2007","journal-title":"Int. Immunol."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"854967","DOI":"10.3389\/fphar.2022.854967","article-title":"PD-1\/PD-L1 Inhibitors in Patients with Preexisting Autoimmune Diseases","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1158\/1535-7163.MCT-14-0983","article-title":"PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy","volume":"14","author":"Patel","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1517\/14728222.12.10.1275","article-title":"Raf Kinase Inhibitory Protein (RKIP): A Physiological Regulator and Future Therapeutic Target","volume":"12","author":"Zeng","year":"2008","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cellsig.2007.07.003","article-title":"Signaling Crossroads: The Function of Raf Kinase Inhibitory Protein in Cancer, the Central Nervous System and Reproduction","volume":"20","author":"Klysik","year":"2008","journal-title":"Cell. Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/43686","article-title":"Suppression of Raf-1 Kinase Activity and MAP Kinase Signalling by RKIP","volume":"401","author":"Yeung","year":"1999","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.3724\/abbs.2022188","article-title":"Cefotetan-Bound Human RKIP Involves in Ras\/Raf1\/MEK\/ERK Signaling Pathway","volume":"54","author":"Guo","year":"2022","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Papale, M., Netti, G.S., Stallone, G., and Ranieri, E. (2022). Understanding Mechanisms of RKIP Regulation to Improve the Development of New Diagnostic Tools. Cancers, 14.","DOI":"10.3390\/cancers14205070"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gabriela-Freitas, P., Pinheiro, J., Raquel-Cunha, A., and Cardoso-Carneiro, D. (2019). Martinho, O. RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer. Biomolecules, 9.","DOI":"10.3390\/biom9120769"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1615\/CritRevOncog.2014011987","article-title":"Survey of Raf Kinase Inhibitor Protein (RKIP) in Multiple Cancer Types","volume":"19","author":"Lamiman","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.imlet.2017.02.006","article-title":"Inflammatory Cytokines IL-17 and TNF-\u03b1 up-Regulate PD-L1 Expression in Human Prostate and Colon Cancer Cells","volume":"184","author":"Wang","year":"2017","journal-title":"Immunol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/PPO.0000000000000059","article-title":"Biochemical Signaling of PD-1 on T Cells and Its Functional Implications","volume":"20","author":"Boussiotis","year":"2014","journal-title":"Cancer J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Patsoukis, N., Duke-Cohan, J.S., Chaudhri, A., Aksoylar, H.-I., Wang, Q., Council, A., Berg, A., Freeman, G.J., and Boussiotis, V.A. (2020). Interaction of SHP-2 SH2 Domains with PD-1 ITSM Induces PD-1 Dimerization and SHP-2 Activation. Commun. Biol., 3.","DOI":"10.1038\/s42003-020-0845-0"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e74276","DOI":"10.7554\/eLife.74276","article-title":"Molecular Features Underlying Differential SHP1\/SHP2 Binding of Immune Checkpoint Receptors","volume":"10","author":"Xu","year":"2021","journal-title":"eLife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13866","DOI":"10.1073\/pnas.231486598","article-title":"PD-1 Immunoreceptor Inhibits B Cell Receptor-Mediated Signaling by Recruiting Src Homology 2-Domain-Containing Tyrosine Phosphatase 2 to Phosphotyrosine","volume":"98","author":"Okazaki","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"220007","DOI":"10.20900\/immunometab20220007","article-title":"Effects of PD-1 Signaling on Immunometabolic Reprogramming","volume":"4","author":"Boussiotis","year":"2022","journal-title":"Immunometabolism"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hofmeyer, K.A., Jeon, H., and Zang, X. (2011). The PD-1\/PD-L1 (B7-H1) Pathway in Chronic Infection-Induced Cytotoxic T Lymphocyte Exhaustion. J. Biomed. Biotechnol., 2011.","DOI":"10.1155\/2011\/451694"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.it.2015.02.007","article-title":"T Cell Metabolic Fitness in Antitumor Immunity","volume":"36","author":"Siska","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1084\/jem.20112741","article-title":"Programmed Cell Death 1 Forms Negative Costimulatory Microclusters That Directly Inhibit T Cell Receptor Signaling by Recruiting Phosphatase SHP2","volume":"209","author":"Yokosuka","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Papa, A., and Pandolfi, P.P. (2019). The PTEN\u2013PI3K Axis in Cancer. Biomolecules, 9.","DOI":"10.20944\/preprints201904.0127.v1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.csbj.2019.03.006","article-title":"Application of PD-1 Blockade in Cancer Immunotherapy","volume":"17","author":"Wu","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1172\/JCI96061","article-title":"PD-L1 on Host Cells Is Essential for PD-L1 Blockade\u2013Mediated Tumor Regression","volume":"128","author":"Tang","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.molcel.2019.09.030","article-title":"Mechanisms Controlling PD-L1 Expression in Cancer","volume":"76","author":"Cha","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"djv303","DOI":"10.1093\/jnci\/djv303","article-title":"PDL1 Regulation by P53 via miR-34","volume":"108","author":"Cortez","year":"2016","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12293","DOI":"10.1073\/pnas.192461099","article-title":"Involvement of PD-L1 on Tumor Cells in the Escape from Host Immune System and Tumor Immunotherapy by PD-L1 Blockade","volume":"99","author":"Iwai","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1146\/annurev-immunol-041015-055318","article-title":"CD8 T Cell Exhaustion during Chronic Viral Infection and Cancer","volume":"37","author":"McLane","year":"2019","journal-title":"Annu. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"715234","DOI":"10.3389\/fimmu.2021.715234","article-title":"CD8+ T Cell Exhaustion in Cancer","volume":"12","author":"Dolina","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.ccell.2018.02.005","article-title":"Tumor-Repopulating Cells Induce PD-1 Expression in CD8+ T Cells by Transferring Kynurenine and AhR Activation","volume":"33","author":"Liu","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4749","DOI":"10.1073\/pnas.1718217115","article-title":"Role of PD-1 during Effector CD8 T Cell Differentiation","volume":"115","author":"Ahn","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40425-018-0316-z","article-title":"Development of PD-1 and PD-L1 Inhibitors as a Form of Cancer Immunotherapy: A Comprehensive Review of Registration Trials and Future Considerations","volume":"6","author":"Gong","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1080\/21645515.2019.1571892","article-title":"PD-1 and PD-L1 in Cancer Immunotherapy: Clinical Implications and Future Considerations","volume":"15","author":"Jiang","year":"2019","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1634\/theoncologist.2018-0686","article-title":"Dual Checkpoint Inhibition with Ipilimumab plus Nivolumab After Progression on Sequential PD-1\/PDL-1 Inhibitors Pembrolizumab and Atezolizumab in a Patient with Lynch Syndrome, Metastatic Colon, and Localized Urothelial Cancer","volume":"24","author":"Winer","year":"2019","journal-title":"Oncologist"},{"key":"ref_53","first-page":"174","article-title":"Purification and Characterization of a Basic 23 kDa Cytosolic Protein from Bovine Brain","volume":"790","author":"Bernier","year":"1984","journal-title":"Biochim. Biophys. Acta BBA-Protein Struct. Mol. Enzymol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1615\/CritRevOncog.2014011929","article-title":"RKIP-Mediated Chemo-Immunosensitization of Resistant Cancer Cells via Disruption of the NF-\u03baB\/Snail\/YY1\/RKIP Resistance-Driver Loop","volume":"19","author":"Bonavida","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"39050","DOI":"10.18632\/oncotarget.5176","article-title":"RKIP Regulates CCL5 Expression to Inhibit Breast Cancer Invasion and Metastasis by Controlling Macrophage Infiltration","volume":"6","author":"Datar","year":"2015","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"23407","DOI":"10.1074\/jbc.M112.363812","article-title":"Raf Kinase Inhibitor Protein (RKIP) Dimer Formation Controls Its Target Switch from Raf1 to G Protein-Coupled Receptor Kinase (GRK) 2","volume":"287","author":"Deiss","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lorenz, K., and Rosner, M.R. (2022). Harnessing RKIP to Combat Heart Disease and Cancer. Cancers, 14.","DOI":"10.3390\/cancers14040867"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.acthis.2013.03.003","article-title":"Raf Kinase Inhibitor Protein (RKIP) and Phospho-RKIP Expression in Melanomas","volume":"115","author":"Cardile","year":"2013","journal-title":"Acta Histochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1128\/MCB.01271-08","article-title":"Raf Kinase Inhibitory Protein Function Is Regulated via a Flexible Pocket and Novel Phosphorylation-Dependent Mechanism","volume":"29","author":"Granovsky","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/S0969-2126(98)00125-7","article-title":"Function from Structure? The Crystal Structure of Human Phosphatidylethanolamine-Binding Protein Suggests a Role in Membrane Signal Transduction","volume":"6","author":"Banfield","year":"1998","journal-title":"Structure"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1615\/CritRevOncog.2014012001","article-title":"RKIP Structure Drives Its Function: A Three-State Model for Regulation of RKIP","volume":"19","author":"Skinner","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nature02158","article-title":"Protein Kinase C Switches the Raf Kinase Inhibitor from Raf-1 to GRK-2","volume":"426","author":"Lorenz","year":"2003","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"13453","DOI":"10.1073\/pnas.1711543114","article-title":"Conserved Salt-Bridge Competition Triggered by Phosphorylation Regulates the Protein Interactome","volume":"114","author":"Skinner","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6405","DOI":"10.1016\/j.febslet.2006.10.054","article-title":"Regulation of RKIP Binding to the N-region of the Raf-1 Kinase","volume":"580","author":"Park","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"24931","DOI":"10.1074\/jbc.M413929200","article-title":"Raf Kinase Inhibitory Protein Regulates Raf-1 but Not B-Raf Kinase Activation","volume":"280","author":"Trakul","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.apsb.2018.01.008","article-title":"Targeting ERK, an Achilles\u2019 Heel of the MAPK Pathway, in Cancer Therapy","volume":"8","author":"Liu","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1615\/CritRevOncog.2014012000","article-title":"Raf Kinase Inhibitory Protein (RKIP) as a Metastasis Suppressor: Regulation of Signaling Networks in Cancer","volume":"19","author":"Yesilkanal","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Huerta-Yepez, S., Yoon, N.K., Hernandez-Cueto, A., Mah, V., Rivera-Pazos, C.M., Chatterjee, D., Vega, M.I., Maresh, E.L., Horvath, S., and Chia, D. (2011). Expression of Phosphorylated Raf Kinase Inhibitor Protein (pRKIP) Is a Predictor of Lung Cancer Survival. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-259"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13014-016-0696-5","article-title":"Prognostic Value of Phosphorylated Raf Kinase Inhibitory Protein at Serine 153 and Its Predictive Effect on the Clinical Response to Radiotherapy in Nasopharyngeal Carcinoma","volume":"11","author":"Li","year":"2016","journal-title":"Radiat. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zaravinos, A., Bonavida, B., Chatzaki, E., and Baritaki, S. (2018). RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact. Cancers, 10.","DOI":"10.3390\/cancers10090287"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Cross-Knorr, S., Lu, S., Perez, K., Guevara, S., Brilliant, K., Pisano, C., Quesenberry, P.J., Resnick, M.B., and Chatterjee, D. (2013). RKIP Phosphorylation and STAT3 Activation Is Inhibited by Oxaliplatin and Camptothecin and Are Associated with Poor Prognosis in Stage II Colon Cancer Patients. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-463"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13046-017-0535-z","article-title":"Overexpression of RKIP and Its Cross-Talk with Several Regulatory Gene Products in Multiple Myeloma","volume":"36","author":"Shvartsur","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Touboul, R., Baritaki, S., Zaravinos, A., and Bonavida, B. (2021). RKIP Pleiotropic Activities in Cancer and Inflammatory Diseases: Role in Immunity. Cancers, 13.","DOI":"10.3390\/cancers13246247"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1128\/MCB.21.21.7207-7217.2001","article-title":"Raf Kinase Inhibitor Protein Interacts with NF-\u03baB-Inducing Kinase and TAK1 and Inhibits NF-\u03baB Activation","volume":"21","author":"Yeung","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2010.10.001","article-title":"Dual Role of NO Donors in the Reversal of Tumor Cell Resistance and EMT: Downregulation of the NF-\u03baB\/Snail\/YY1\/RKIP Circuitry","volume":"24","author":"Bonavida","year":"2011","journal-title":"Nitric Oxide"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10555-012-9365-9","article-title":"Raf Kinase Inhibitor Protein (RKIP) in Cancer","volume":"31","author":"Yeung","year":"2012","journal-title":"Cancer Metastasis Rev."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Cessna, H., Baritaki, S., Zaravinos, A., and Bonavida, B. (2022). The Role of RKIP in the Regulation of EMT in the Tumor Microenvironment. Cancers, 14.","DOI":"10.3390\/cancers14194596"},{"key":"ref_78","first-page":"241","article-title":"The Activated NF-\u0138B-Snail-RKIP Circuitry in Cancer Regulates Both the Metastatic Cascade and Resistance to Apoptosis by Cytotoxic Drugs","volume":"29","author":"Wu","year":"2009","journal-title":"Crit. Rev. Oncog."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1172\/JCI35213","article-title":"Stat3 Mediates Myeloid Cell\u2013Dependent Tumor Angiogenesis in Mice","volume":"118","author":"Kujawski","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STATs in Cancer Inflammation and Immunity: A Leading Role for STAT3","volume":"9","author":"Yu","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"13079","DOI":"10.1073\/pnas.1311557110","article-title":"Regulation of Adipose Tissue T Cell Subsets by Stat3 Is Crucial for Diet-Induced Obesity and Insulin Resistance","volume":"110","author":"Priceman","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrc3818","article-title":"Revisiting STAT3 Signalling in Cancer: New and Unexpected Biological Functions","volume":"14","author":"Yu","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1615\/CritRevOncog.2014011922","article-title":"Regulation of the MAPK Pathway by Raf Kinase Inhibitory Protein","volume":"19","author":"Vandamme","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e44951","DOI":"10.15252\/embr.201744951","article-title":"RKIP Mediates Autoimmune Inflammation by Positively Regulating IL-17R Signaling","volume":"19","author":"Lin","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Bach, V.N., Ding, J., Yeung, M., Conrad, T., Odeh, H.N., Cubberly, P., Figy, C., Ding, H.-F., Trumbly, R., and Yeung, K.C. (2022). A Negative Regulatory Role for RKIP in Breast Cancer Immune Response. Cancers, 14.","DOI":"10.3390\/cancers14153605"},{"key":"ref_86","unstructured":"Christofi, T., and Zaravinos, A. (2020). Prognostic and Therapeutic Applications of RKIP in Cancer, Elsevier."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1615\/CritRevOncog.2018027211","article-title":"A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics","volume":"23","author":"Wang","year":"2018","journal-title":"Crit. Rev. Oncog."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1158\/0008-5472.CAN-14-3394","article-title":"Metastasis Suppressors Regulate the Tumor Microenvironment by Blocking Recruitment of Prometastatic Tumor-Associated Macrophages","volume":"75","author":"Frankenberger","year":"2015","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1615\/CritRevOncog.2014011950","article-title":"Interactions of RKIP with Inflammatory Signaling Pathways","volume":"19","author":"Zhao","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"110894","DOI":"10.1016\/j.intimp.2023.110894","article-title":"Crosstalk between PD-L1 and Jak2-Stat3\/MAPK-AP1 Signaling Promotes Oral Cancer Progression, Invasion and Therapy Resistance","volume":"124","author":"Jha","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6262","DOI":"10.1038\/s41467-020-19810-w","article-title":"PD-L1 Blockade in Combination with Inhibition of MAPK Oncogenic Signaling in Patients with Advanced Melanoma","volume":"11","author":"Ribas","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/path.5280","article-title":"MAPK Pathway Activity Plays a Key Role in PD-L1 Expression of Lung Adenocarcinoma Cells","volume":"249","author":"Stutvoet","year":"2019","journal-title":"J. Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13045-020-01027-5","article-title":"Regulation of PD-L1 Expression in the Tumor Microenvironment","volume":"14","author":"Yi","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1192861","DOI":"10.3389\/fimmu.2023.1192861","article-title":"Regulation of PD-L1 Expression in Non\u2013Small Cell Lung Cancer by Interleukin-1\u03b2","volume":"14","author":"Hirayama","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"21810","DOI":"10.1038\/srep21810","article-title":"Specific Regulation of PRMT1 Expression by PIAS1 and RKIP in BEAS-2B Epithelia Cells and HFL-1 Fibroblasts in Lung Inflammation","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"708","DOI":"10.4049\/jimmunol.1203486","article-title":"RKIP Contributes to IFN-\u03b3 Synthesis by CD8+ T Cells after Serial TCR Triggering in Systemic Inflammatory Response Syndrome","volume":"191","author":"Wright","year":"2013","journal-title":"J. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1172\/JCI91190","article-title":"IFN-\u03b3\u2013Related mRNA Profile Predicts Clinical Response to PD-1 Blockade","volume":"127","author":"Ayers","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12974-018-1330-2","article-title":"The IFN-\u03b3\/PD-L1 Axis between T Cells and Tumor Microenvironment: Hints for Glioma Anti-PD-1\/PD-L1 Therapy","volume":"15","author":"Qian","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"114301","DOI":"10.1016\/j.ejmech.2022.114301","article-title":"Development of Inhibitors Targeting Glycogen Synthase Kinase-3\u03b2 for Human Diseases: Strategies to Improve Selectivity","volume":"236","author":"Wei","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1158\/0008-5472.CAN-10-3102","article-title":"Raf Kinase Inhibitor Protein RKIP Enhances Signaling by Glycogen Synthase Kinase-3\u03b2","volume":"71","author":"Bitar","year":"2011","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.tibs.2009.10.002","article-title":"GSK3: A Multifaceted Kinase in Wnt Signaling","volume":"35","author":"Wu","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s13238-019-00673-x","article-title":"Targeting Oncogenic SOX2 in Human Cancer Cells: Therapeutic Application","volume":"11","author":"Zhang","year":"2020","journal-title":"Protein Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.3892\/or.2017.5523","article-title":"Transcriptional Activation of PD-L1 by Sox2 Contributes to the Proliferation of Hepatocellular Carcinoma Cells","volume":"37","author":"Zhong","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1158\/1541-7786.MCR-21-0373","article-title":"RKIP Induction Promotes Tumor Differentiation via SOX2 Degradation in NF2-Deficient Conditions","volume":"20","author":"Cho","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"433","DOI":"10.21037\/atm.2020.03.195","article-title":"MicroRNA-18a Induces Epithelial-Mesenchymal Transition like Cancer Stem Cell Phenotype via Regulating RKIP Pathway in Pancreatic Cancer","volume":"8","author":"Kang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Lee, S., Wottrich, S., and Bonavida, B. (2017). Crosstalks between Raf-Kinase Inhibitor Protein and Cancer Stem Cell Transcription Factors (Oct4, KLF4, Sox2, Nanog). Tumor Biol., 39.","DOI":"10.1177\/1010428317692253"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.3389\/fonc.2019.01230","article-title":"The Two Sides of YY1 in Cancer: A Friend and a Foe","volume":"9","author":"Sarvagalla","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1038\/onc.2009.214","article-title":"Inhibition of Epithelial to Mesenchymal Transition in Metastatic Prostate Cancer Cells by the Novel Proteasome Inhibitor, NPI-0052: Pivotal Roles of Snail Repression and RKIP Induction","volume":"28","author":"Baritaki","year":"2009","journal-title":"Oncogene"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.drup.2019.04.001","article-title":"YY1 Regulates Cancer Cell Immune Resistance by Modulating PD-L1 Expression","volume":"43","author":"Hays","year":"2019","journal-title":"Drug Resist. Updates"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Cai, H., Yan, L., Liu, N., Xu, M., and Cai, H. (2020). IFI16 Promotes Cervical Cancer Progression by Upregulating PD-L1 in Immunomicroenvironment through STING-TBK1-NF-kB Pathway. Biomed. Pharmacother., 123.","DOI":"10.1016\/j.biopha.2019.109790"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Huang, G., Wen, Q., Zhao, Y., Gao, Q., and Bai, Y. (2013). NF-\u03baB Plays a Key Role in Inducing CD274 Expression in Human Monocytes after Lipopolysaccharide Treatment. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061602"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1158\/0008-5472.CAN-17-1636","article-title":"MUC1-C Induces PD-L1 and Immune Evasion in Triple-Negative Breast Cancer","volume":"78","author":"Maeda","year":"2018","journal-title":"Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Gowrishankar, K., Gunatilake, D., Gallagher, S.J., Tiffen, J., Rizos, H., and Hersey, P. (2015). Inducible but Not Constitutive Expression of PD-L1 in Human Melanoma Cells Is Dependent on Activation of NF-\u03baB. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123410"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"14115","DOI":"10.1038\/s41598-020-70514-z","article-title":"Programmed Death Ligand-1 (PD-L1) Expression in Meningioma; Prognostic Significance and Its Association with Hypoxia and NFKB2 Expression","volume":"10","author":"Karimi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"9997","DOI":"10.1002\/jcb.27329","article-title":"LPS Promotes the Expression of PD-L1 in Gastric Cancer Cells through NF-\u03baB Activation","volume":"119","author":"Li","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"4200","DOI":"10.1093\/bioinformatics\/btz210","article-title":"TISIDB: An Integrated Repository Portal for Tumor\u2013Immune System Interactions","volume":"35","author":"Ru","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An Enhanced Web Server for Large-Scale Expression Profiling and Interactive Analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Daily, K., Patel, V.R., Rigor, P., Xie, X., and Baldi, P. (2011). MotifMap: Integrative Genome-Wide Maps of Regulatory Motif Sites for Model Species. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-495"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1093\/bioinformatics\/btx087","article-title":"MotifMap-RNA: A Genome-Wide Map of RBP Binding Sites","volume":"33","author":"Liu","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/bioinformatics\/btn605","article-title":"MotifMap: A Human Genome-Wide Map of Candidate Regulatory Motif Sites","volume":"25","author":"Xie","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/0092-8674(92)90554-P","article-title":"The High Mobility Group Protein HMG I(Y) Is Required for NF-KB-Dependent Virus Induction of the Human IFN-P Gene","volume":"71","author":"Maniatis","year":"1992","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/\u03b2-Catenin Signaling in Development and Disease","volume":"127","author":"Clevers","year":"2006","journal-title":"Cell"},{"key":"ref_123","first-page":"147","article-title":"American Ginseng (Panax quinquefolius L.) Extract Alters Mitogen-Activated Protein Kinase Cell Signaling and Inhibits Proliferation of MCF-7 Cells","volume":"6","author":"King","year":"2007","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3892\/ijo.2012.1686","article-title":"(-)-Epigallocatechin 3-Gallate Inhibits Invasion by Inducing the Expression of Raf Kinase Inhibitor Protein in AsPC-1 Human Pancreatic Adenocarcinoma Cells through the Modulation of Histone Deacetylase Activity","volume":"42","author":"Kim","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1078642","DOI":"10.3389\/fnut.2022.1078642","article-title":"Targeting a Transcription Factor NF-\u03baB by Green Tea Catechins Using in Silico and in Vitro Studies in Pancreatic Cancer","volume":"9","author":"Suhail","year":"2023","journal-title":"Front. Nutr."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1038\/sj.onc.1208349","article-title":"Cellular and Molecular Signal Transduction Pathways Modulated by Rituximab (Rituxan, Anti-CD20 mAb) in Non-Hodgkin\u2019s Lymphoma: Implications in Chemosensitization and Therapeutic Intervention","volume":"24","author":"Jazirehi","year":"2005","journal-title":"Oncogene"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1158\/1940-6207.CAPR-11-0318","article-title":"Didymin Induces Apoptosis by Inhibiting N-Myc and Upregulating RKIP in Neuroblastoma","volume":"5","author":"Singhal","year":"2012","journal-title":"Cancer Prev. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4161\/cbt.27223","article-title":"Dihydroartemisinin Induces Apoptosis of Cervical Cancer Cells via Upregulation of RKIP and Downregulation of Bcl-2","volume":"15","author":"Hu","year":"2014","journal-title":"Cancer Biol. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"722331","DOI":"10.3389\/fonc.2021.722331","article-title":"Dihydroartemisinin: A Potential Drug for the Treatment of Malignancies and Inflammatory Diseases","volume":"11","author":"Yu","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.intimp.2016.11.028","article-title":"Didymin Ameliorates Hepatic Injury through Inhibition of MAPK and NF-\u03baB Pathways by up-Regulating RKIP Expression","volume":"42","author":"Huang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1158\/1535-7163.MCT-17-1210","article-title":"Loss of NF2 Induces TGF\u03b2 Receptor 1\u2013Mediated Noncanonical and Oncogenic TGF\u03b2 Signaling: Implication of the Therapeutic Effect of TGF\u03b2 Receptor 1 Inhibitor on NF2 Syndrome","volume":"17","author":"Cho","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.redox.2015.08.013","article-title":"Nitric Oxide-Mediated Sensitization of Resistant Tumor Cells to Apoptosis by Chemo-Immunotherapeutics","volume":"6","author":"Bonavida","year":"2015","journal-title":"Redox Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.canlet.2017.01.040","article-title":"Metronomic Chemotherapy and Immunotherapy in Cancer Treatment","volume":"400","author":"Chen","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4800","DOI":"10.1002\/anie.201916039","article-title":"Homogeneous, Low-volume, Efficient, and Sensitive Quantitation of Circulating Exosomal PD-L1 for Cancer Diagnosis and Immunotherapy Response Prediction","volume":"59","author":"Huang","year":"2020","journal-title":"Angew. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41401-020-0366-x","article-title":"Small Molecule Inhibitors Targeting the PD-1\/PD-L1 Signaling Pathway","volume":"42","author":"Wu","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-pathol-042020-042741","article-title":"Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance","volume":"16","author":"Bagchi","year":"2021","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"562315","DOI":"10.3389\/fonc.2021.562315","article-title":"Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis","volume":"11","author":"Chen","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.7150\/thno.80091","article-title":"Strategies Targeting PD-L1 Expression and Associated Opportunities for Cancer Combination Therapy","volume":"13","author":"Yin","year":"2023","journal-title":"Theranostics"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13045-021-01045-x","article-title":"The Construction, Expression, and Enhanced Anti-Tumor Activity of YM101: A Bispecific Antibody Simultaneously Targeting TGF-\u03b2 and PD-L1","volume":"14","author":"Yi","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1600-065X.2007.00565.x","article-title":"\u2018Yin-Yang\u2019 Functions of TGF-\u03b2 and Tregs in Immune Regulation","volume":"220","author":"Wan","year":"2007","journal-title":"Immunol. Rev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1158\/1078-0432.CCR-16-2601","article-title":"PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma","volume":"23","author":"Melaiu","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.humpath.2016.07.007","article-title":"PD-L1 Expression Is Associated with Epithelial-to-Mesenchymal Transition in Adenocarcinoma of the Lung","volume":"58","author":"Kim","year":"2016","journal-title":"Hum. Pathol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"29428","DOI":"10.18632\/oncotarget.15204","article-title":"Didymin: An Orally Active Citrus Flavonoid for Targeting Neuroblastoma","volume":"8","author":"Singhal","year":"2017","journal-title":"Oncotarget"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1556-0864(15)31506-9","article-title":"The Ras\/Raf\/MAPK Pathway","volume":"1","author":"Molina","year":"2006","journal-title":"J. Thorac. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.cellsig.2013.02.005","article-title":"RKIP Regulates MAP Kinase Signaling in Cells with Defective B-Raf Activity","volume":"25","author":"Zeng","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1038\/sj.onc.1208435","article-title":"RKIP Downregulates B-Raf Kinase Activity in Melanoma Cancer Cells","volume":"24","author":"Park","year":"2005","journal-title":"Oncogene"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"E9859","DOI":"10.1073\/pnas.1805474115","article-title":"Raf Kinase Inhibitor Protein Negatively Regulates Fc\u03b5RI-Mediated Mast Cell Activation and Allergic Response","volume":"115","author":"Lin","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Lakshmi, S.P., Reddy, A.T., Kodidhela, L.D., and Varadacharyulu, N.C. (2020). The Tea Catechin Epigallocatechin Gallate Inhibits NF-\u03baB-Mediated Transcriptional Activation by Covalent Modification. Arch. Biochem. Biophys., 695.","DOI":"10.1016\/j.abb.2020.108620"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"8376","DOI":"10.1158\/0008-5472.CAN-09-1069","article-title":"Pivotal Roles of Snail Inhibition and RKIP Induction by the Proteasome Inhibitor NPI-0052 in Tumor Cell Chemoimmunosensitization","volume":"69","author":"Baritaki","year":"2009","journal-title":"Cancer Res."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Lei, Q., Wang, D., Sun, K., Wang, L., and Zhang, Y. (2020). Resistance Mechanisms of Anti-PD1\/PDL1 Therapy in Solid Tumors. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00672"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Vivarelli, S., Falzone, L., Grillo, C.M., Bonavida, B., Crimi, C., La Mantia, I., and Libra, M. (2022). Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer. Cancers, 14.","DOI":"10.3390\/cancers14040922"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1615\/CritRevOncog.v16.i3-4.20","article-title":"Mechanisms of Yin Yang 1 in Oncogenesis: The Importance of Indirect Effects","volume":"16","author":"Atchison","year":"2011","journal-title":"Crit. Rev. Oncog."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s00432-021-03510-z","article-title":"Resveratrol Induces PD-L1 Expression through Snail-Driven Activation of Wnt Pathway in Lung Cancer Cells","volume":"147","author":"Yang","year":"2021","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 Is a Novel Direct Target of HIF-1\u03b1, and Its Blockade under Hypoxia Enhanced MDSC-Mediated T Cell Activation","volume":"211","author":"Noman","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11010-020-03788-6","article-title":"HIF-1\u03b1 and RKIP: A Computational Approach for Pancreatic Cancer Therapy","volume":"472","author":"Srivani","year":"2020","journal-title":"Mol. Cell. Biochem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1186\/s13014-020-01696-z","article-title":"Prognostic Value of PD-L1 Expression in Patients with Unresectable Stage III Non-Small Cell Lung Cancer Treated with Chemoradiotherapy","volume":"15","author":"Vrankar","year":"2020","journal-title":"Radiat. Oncol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e15176","DOI":"10.1200\/JCO.2020.38.15_suppl.e15176","article-title":"Distribution of PD-L1 Expression Level across Major Tumor Types","volume":"38","author":"Xu","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13045-020-00949-4","article-title":"The MAPK and AMPK Signalings: Interplay and Implication in Targeted Cancer Therapy","volume":"13","author":"Yuan","year":"2020","journal-title":"J. Hematol. Oncol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/10\/864\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:44:02Z","timestamp":1760107442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/10\/864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,17]]},"references-count":159,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["cells13100864"],"URL":"https:\/\/doi.org\/10.3390\/cells13100864","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,17]]}}}