FOXP3 and CTLA4 overexpression in multiple myeloma bone marrow as a sign of accumulation of CD4+ T regulatory cells
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INTRODUCTION: Multiple myeloma (MM) development involves a series of genetic abnormalities and changes in the bone marrow (BM) microenvironment, favoring the growth of the tumor and failure of local immune control. T regulatory (Treg) cells play an important role in dampening anti-tumor immune responses while T-helper-17 (Th17) cells seem to be critical for the eradication of malignant cells. The aim of our study was to characterize the expression of Treg- and Th17-related genes in total myeloma BM samples to assess their role as biomarkers, prognostic factors, and possible therapeutic targets in this incurable disease. METHODS: Expression of markers for Treg (FOXP3, CTLA4) and Th17 cells (RORγt) was determined by quantitative real-time PCR in BM aspirates of 46 MM patients, four patients with monoclonal gammopathy of undetermined significance, five solitary plasmacytomas, and five healthy BM donors. Gene expression was evaluated regarding an influence on the patients' overall survival (OS). RESULTS: FOXP3 and CTLA4 presented a sixfold (p = 0.02) and 30-fold higher expression (p = 0.03), respectively, in MM patients than in controls. RORγt expression was similar in MM patients and controls. Median OS of MM patients was 16.8 (range 4.5-29.1) months, and international staging system was the only independent prognostic factor for patients survival. CONCLUSIONS: Overexpression of FOXP3 and CTLA4 in total BM samples suggests a local accumulation of immunosuppressive Tregs, the MM tumor environment, possibly dampening anti-tumor host immune responses. Therapeutic approaches targeting Treg cells and restoring local anti-tumor immunity may provide new treatment strategies for this incurable malignancy.
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BM samples from newly diagnosed MM patients showed upregulation of CTLA-4, according to a study by Braga et al.
“BM samples from newly diagnosed MM patients showed upregulation of CTLA-4, according to a study by Braga et al. [220].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [220]
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Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873 · see citing works
Chen, W., Jin, W., Hardegen, N. J., Lei, K.-J., Li, L., Marinos, N. J., McGrady, G., & Wahl, S. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030152 · Cited by 4,678 · see citing works
International Staging System for Multiple Myeloma
Greipp, P. R., Miguel, J. S., Durie, B. G. M., Crowley, J. J., Barlogie, B., Bladé, J., Boccadoro, M., Child, J. A., Avet-Loiseau, H., Kyle, R. A., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.242 · Cited by 2,974 · see citing works
The International Myeloma Working Group (2003) · British Journal of Haematology · doi:10.1046/j.1365-2141.2003.04355.x · Cited by 2,367 · see citing works
TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function
Zhou, L., Lopes, J. E., Chong, M. M. W., Ivanov, I. I., Min, R., Victora, G. D., Shen, Y., Du, J., Rubtsov, Y. P., Rudensky, A. Y., et al. (2008) · Nature · doi:10.1038/nature06878 · Cited by 1,859 · see citing works
T Helper 17 Lineage Differentiation Is Programmed by Orphan Nuclear Receptors RORα and RORγ
Yang, X. O., Pappu, B. P., Nurieva, R., Akimzhanov, A., Kang, H. S., Chung, Y., Ma, L., Shah, B., Panopoulos, A. D., Schluns, K. S., et al. (2008) · Immunity · doi:10.1016/j.immuni.2007.11.016 · Cited by 1,605 · see citing works
Inducing and expanding regulatory T cell populations by foreign antigen
Kretschmer, K., Apostolou, I., Hawiger, D., Khazaie, K., Nussenzweig, M. C., & von Boehmer, H. (2005) · Nature Immunology · doi:10.1038/ni1265 · Cited by 1,240 · see citing works
Molecular Antagonism and Plasticity of Regulatory and Inflammatory T Cell Programs
Yang, X. O., Nurieva, R., Martínez, G., Kang, H. S., Chung, Y., Pappu, B. P., Shah, B., Chang, S. H., Schluns, K. S., Watowich, S. S., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.007 · Cited by 1,129 · see citing works
Allan, S. E., Crome, S. Q., Crellin, N. K., Passerini, L., Steiner, T. S., Bacchetta, R., Roncarolo, M. G., & Levings, M. K. (2007) · International Immunology · doi:10.1093/intimm/dxm014 · Cited by 872 · cited 1× · see citing works
“Despite FOXP3 being considered the most specific marker for naturally occurring CD4+ CD25+ Tregs, dividing activated T effector cells (Teff cells) can express FOXP3 transiently, and at significantly lower levels than suppressive Tregs [24].”
BackgroundKryczek, I., Banerjee, M., Cheng, P. J., Vatan, L., Szeliga, W., Wei, S., Huang, E. H., Finlayson, E. V. A., Simeone, D. M., Welling, T. H., et al. (2009) · Blood · doi:10.1182/blood-2009-03-208249 · Cited by 814 · see citing works
Regulatory T cells and mechanisms of immune system control
O’Garra, A., & Vieira, P. (2004) · Nature Medicine · doi:10.1038/nm0804-801 · Cited by 809 · see citing works
Beyer, M., & Schultze, J. L. (2006) · Blood · doi:10.1182/blood-2006-02-002774 · Cited by 729 · see citing works
Sharma, M. D., Hou, D., Liu, Y., Koni, P. A., Metz, R. A., Chandler, P., Mellor, A. L., He, Y., & Munn, D. H. (2009) · Blood · doi:10.1182/blood-2008-12-195354 · Cited by 406 · see citing works
Rezvani, K., Mielke, S., Ahmadzadeh, M., Kilical, Y., Savani, B. N., Zeilah, J., Keyvanfar, K., Montero, A., Hensel, N. F., Kurlander, R. J., et al. (2006) · Blood · doi:10.1182/blood-2006-02-003996 · Cited by 368 · see citing works
PRABHALA, R. H., Pelluru, D., Fulciniti, M., Prabhala, H. K., Nanjappa, P., Song, W., Pai, C., Amin, S. B., Tai, Y., Richardson, P. G. G., et al. (2010) · Blood · doi:10.1182/blood-2009-10-246660 · Cited by 350 · see citing works
Yuan, J. D., Gnjatic, S., Li, H., Powel, S., Gallardo, H. F., Ritter, E., Ku, G. Y., Jungbluth, A. A., Segal, N. H., Rasalan, T. S., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810114105 · Cited by 346 · see citing works
Immunodeficiency and immunotherapy in multiple myeloma
Pratt, G., Goodyear, O. C., & Moss, P. A. H. (2007) · British Journal of Haematology · doi:10.1111/j.1365-2141.2007.06705.x · Cited by 342 · see citing works
Beyer, M., Kochanek, M., Giese, T., Endl, E., Weihrauch, M. R., Knolle, P. A., Claßen, S., & Schultze, J. L. (2006) · Blood · doi:10.1182/blood-2005-09-3671 · Cited by 301 · see citing works
Natural and Induced T Regulatory Cells in Cancer
Adeegbe, D. O., & Nishikawa, H. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00190 · Cited by 248 · see citing works
Dysfunctional T regulatory cells in multiple myeloma
PRABHALA, R. H., Neri, P. E., Bae, J. E., Tassone, P., Shammas, M. A., Allam, C. K., Daley, J. F., Chauhan, D., Blanchard, E. M., Thatte, H. S., et al. (2005) · Blood · doi:10.1182/blood-2005-08-3101 · Cited by 236 · see citing works
Dhodapkar, K. M., Barbuto, S., Matthews, P., Kukreja, A., Mazumder, A., Vesole, D. H., Jagannath, S., & Dhodapkar, M. V. (2008) · Blood · doi:10.1182/blood-2008-03-143222 · Cited by 215 · see citing works
Magalhaes, R. J., Vídriales, M., Paiva, B., Fernández, C., García‐Sánz, R., Mateos, M., Gutierrez, N. C., Lécrevisse, Q., Blanco, J. F., Hernández‐Rivas, J. M., et al. (2012) · Haematologica · doi:10.3324/haematol.2012.067272 · Cited by 172 · see citing works
Maruyama, T., Kono, K., Mizukami, Y., Kawaguchi, Y., Mimura, K., Watanabe, M., Izawa, S., & Fujii, H. (2010) · Cancer Science · doi:10.1111/j.1349-7006.2010.01624.x · Cited by 163 · see citing works
Feyler, S., Lilienfeld‐Toal, M. V., Jarmin, S. J., Marles, L., Rawstron, A. C., Ashcroft, A. J., Owen, R. G., Selby, P. J., & Cook, G. (2009) · British Journal of Haematology · doi:10.1111/j.1365-2141.2008.07530.x · Cited by 145 · see citing works
Giannopoulos, K., Kamińska, W., Hus, I., & Dmoszyńska, A. (2012) · British Journal of Cancer · doi:10.1038/bjc.2011.575 · Cited by 124 · see citing works
Raja, K. R. M., Říhová, L., Zahradová, L., Klincová, M., Penka, M., & Hájek, R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047077 · Cited by 121 · see citing works
Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients.
Andrade, V. C. C., Vettore, A. L., Felix, R. S., Almeida, M. S. S., de Carvalho, F., de Oliveira, J. S. R., Chauffaille, M. D. L. L. F., Andriolo, A., Caballero, O. L., Zago, M. A., et al. (2008) · PubMed Central · Cited by 120 · see citing works
Self-citationSaini, C., Ramesh, V., & Nath, I. (2014) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002639 · Cited by 61 · see citing works
Significantly reduced regulatory T cell population in patients with untreated multiple myeloma
Gupta, R., Ganesan, P., Hakim, M., Verma, R. K., Sharma, A., & Kumar, L. (2010) · Leukemia Research · doi:10.1016/j.leukres.2010.11.010 · Cited by 55 · see citing works
Felix, R. S., Colleoni, G. W. B., Caballero, O. L., Yamamoto, M., Almeida, M. S. S., Andrade, V. C. C., Chauffaille, M. D. L. L. F., Silva, W. A., Begnami, M. D., Soares, F. A., et al. (2009) · Cancer Letters · doi:10.1016/j.canlet.2008.12.022 · Cited by 55 · see citing works
Self-citationT Regulatory Cells in Cord Blood—FOXP3 Demethylation as Reliable Quantitative Marker
Liu, J., Lluis, A., Illi, S., Layland, L. E., Olek, S., von Mutius, E., & Schaub, B. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013267 · Cited by 54 · see citing works
Hungria, V., Maiolino, Â., Martınez, G., Colleoni, G. W. B., Coelho, É., Rocha, L., Nunes, R., Bittencourt, R., de Oliveira, L. C. O., Faria, R. M. O., et al. (2008) · Haematologica · doi:10.3324/haematol.11637 · Cited by 45 · see citing works
Self-citationLi, L., Patsoukis, N., Petkova, V., & Boussiotis, V. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045115 · Cited by 44 · see citing works
Prognostic Impact of Cancer Testis Antigens Expression in Advanced Stage Multiple Myeloma Patients.
Andrade, V. C. C., Vettore, A. L., Almeida, M. S. S., de Oliveira, J. S. R., Chauffaille, M. D. L. L. F., Yamamoto, M., Andriolo, A., Felix, R. S., de Carvalho, F., Caballero, O. L., et al. (2007) · Blood · doi:10.1182/blood.v110.11.4733.4733 · Cited by 37 · see citing works
Self-citationGuichelaar, T., Emmelot, M. E., Rozemuller, H., Martini, B., Groen, R. W. J., Storm, G., Lokhorst, H. M., Martens, A. C., & Mutis, T. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2177 · Cited by 28 · see citing works
CD4+CD25highFoxP3+ Regulatory T-cells in Hematologic Diseases
Moon, H., Kim, B. H., Park, C. M., Hur, M., Yun, Y., Kim, S., & Lee, M. H. (2011) · Annals of Laboratory Medicine · doi:10.3343/kjlm.2011.31.4.231 · Cited by 25 · see citing works
Ayukawa, H., Matsubara, T., KANEKO, M., HASEGAWA, M., Ichiyama, T., & Furukawa, S. (2004) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2004.02502.x · Cited by 22 · see citing works
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Cited by
Sorted by citations
Cho, S., Anderson, K. C., & Tai, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01821 · Cited by 296 · see citing works
Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies
Wang, H., Kaur, G., Sankin, A. I., Chen, F., Guan, F., & Zang, X. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0746-1 · Cited by 204 · see citing works
Immunogenic Cell Death and Immunotherapy of Multiple Myeloma
del Valle, A. S., Anel, A., Naval, J., & Marzo, I. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00050 · Cited by 196 · see citing works
Checkpoint inhibitors in hematological malignancies
Ok, C. Y., & Young, K. H. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0474-3 · Cited by 136 · see citing works
The correlations between IL-17 vs. Th17 cells and cancer patient survival: a systematic review
Punt, S., Langenhoff, J. M., Putter, H., Fleuren, G. J., Gorter, A., & Jordanova, E. S. (2015) · OncoImmunology · doi:10.4161/2162402x.2014.984547 · Cited by 116 · see citing works
Blocking IFNAR1 inhibits multiple myeloma–driven Treg expansion and immunosuppression
Kawano, Y., Zavidij, O., Park, J., Moschetta, M., Kokubun, K., Mouhieddine, T. H., Manier, S., Mishima, Y., Murakami, N., Bustoros, M. W., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci88169 · Cited by 113 · see citing works
Tai, Y., Lin, L., Xing, L., Cho, S., Yu, T., Acharya, C., Wen, K., Hsieh, P. A., Dulos, J., van Elsas, A., et al. (2018) · Leukemia · doi:10.1038/s41375-018-0242-6 · Cited by 89 · see citing works
Actors on the Scene: Immune Cells in the Myeloma Niche
Leone, P., Solimando, A. G., Malerba, E., Fasano, R., Buonavoglia, A., Pappagallo, F., Re, V. D., Argentiero, A., Silvestris, N., Vacca, A., et al. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.599098 · Cited by 72 · see citing works
Emerging biomarkers in Multiple Myeloma: A review
Gupta, N., Sharma, A., & Sharma, A. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.12.026 · Cited by 67 · see citing works
Osteoclast Immunosuppressive Effects in Multiple Myeloma: Role of Programmed Cell Death Ligand 1
Tai, Y., Cho, S., & Anderson, K. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01822 · Cited by 67 · see citing works
Díaz-Tejedor, A., Lorenzo-Mohamed, M., Puig, N., García‐Sánz, R., Mateos, M., Garayoa, M., & Paíno, T. (2021) · Cancers · doi:10.3390/cancers13061353 · Cited by 65 · see citing works
Retinoic Acid Receptor-Related Orphan Receptors: Critical Roles in Tumorigenesis
Fan, J., Lv, Z., Yang, G., Liao, T. T., Xu, J., Wu, F., Huang, Q., Guo, M., Hu, G., Zhou, M. L., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01187 · Cited by 64 · see citing works
Immunogenic Cell Death in Hematological Malignancy Therapy
Liu, Z., Xu, X., Liu, K., Zhang, J., Ding, D., & Fu, R. (2023) · Advanced Science · doi:10.1002/advs.202207475 · Cited by 63 · see citing works
Immune-based therapies in the management of multiple myeloma
Zanwar, S., Nandakumar, B. N., & Kumar, S. K. (2020) · Blood Cancer Journal · doi:10.1038/s41408-020-00350-x · Cited by 63 · see citing works
Kondo, Y., & Shimosegawa, T. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16023307 · Cited by 56 · see citing works
Yoshida, N., Kinugasa, T., Miyoshi, H., Sato, K., Yuge, K., Ohchi, T., Fujino, S., Shiraiwa, S., Katagiri, M., Akagi, Y., et al. (2016) · Annals of Surgical Oncology · doi:10.1245/s10434-015-4923-3 · Cited by 49 · see citing works
Cytokine profile in multiple myeloma
Jasrotia, S., Gupta, R., Sharma, A., Halder, A., & Kumar, L. (2020) · Cytokine · doi:10.1016/j.cyto.2020.155271 · Cited by 51 · see citing works
Hyperfunction of CD4 CD25 regulatory T cells in de novo acute myeloid leukemia
Wan, Y., Zhang, C., Xu, Y., Wang, M., Rao, Q., Xing, H., Tian, Z., Tang, K., Mi, Y., Wang, Y., et al. (2020) · BMC Cancer · doi:10.1186/s12885-020-06961-8 · Cited by 51 · see citing works
Dahlhoff, J., Manz, H., Steinfatt, T., Tascon, J. D., Seebacher, E., Schneider, T., Wilnit, A., Mokhtari, Z., Tabares, P., Böckle, D., et al. (2021) · Leukemia · doi:10.1038/s41375-021-01422-y · Cited by 46 · see citing works
Desantis, V., Savino, F. D., Scaringella, A., Potenza, M. A., Nacci, C., Frassanito, M. A., Vacca, A., & Montagnani, M. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11092513 · Cited by 45 · see citing works
Chung, D. J., Sharma, S., Rangesa, M., DeWolf, S., Elhanati, Y., Perica, K., & Young, J. W. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021005941 · Cited by 42 · see citing works
Immune checkpoint inhibitors for multiple myeloma immunotherapy
Liu, Z., Xu, X., Liu, H., Zhao, X., Yang, C., & Fu, R. (2023) · Experimental Hematology & Oncology · doi:10.1186/s40164-023-00456-5 · Cited by 40 · see citing works
Gong, T., Wang, C., Yuan, J., Yu, L., Gu, J., Zhao, B., Li, Z., Jia, X., Feng, L., & Liu, S. (2015) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2015/630760 · Cited by 39 · see citing works
Wu, M. C., Chen, X., Lou, J., Zhang, S., Zhang, X., Huang, L., Sun, R., Huang, P., Pan, S., & Wang, F. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.04.004 · Cited by 38 · see citing works
Predictive Role of Immune Profiling for Survival of Multiple Myeloma Patients
Zhaoyun, L., & Fu, R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.663748 · Cited by 38 · see citing works
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Ho, M., Goh, C. Y., Patel, A. S., Staunton, S., O’Connor, R., Godeau, M., & Bianchi, G. (2020) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2020.05.026 · Cited by 38 · see citing works
Xing, K., Zhang, S., Xu, J., Liu, G., Zhang, L., Xie, E., Li, G., Li, D., Sun, R., Wang, F., et al. (2016) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-016-1825-6 · Cited by 35 · see citing works
Treating Multiple Myeloma in the Context of the Bone Marrow Microenvironment
Ho, M., Xiao, A. H., Yi, D., Zanwar, S., & Bianchi, G. (2022) · Current Oncology · doi:10.3390/curroncol29110705 · Cited by 34 · see citing works
Immunological Prognostic Factors in Multiple Myeloma
Bębnowska, D., Hrynkiewicz, R., Grywalska, E., Pasiarski, M., Sosnowska‐Pasiarska, B., Smarz-Widelska, I., Góźdź, S. S., Roliński, J., & Niedźwiedzka‐Rystwej, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073587 · Cited by 32 · see citing works
Rostamzadeh, D., Haghshenas, M. R., Daryanoosh, F., Samadi, M., Hosseini, A., Ghaderi, A. A., Mojtahedi, Z., & Babaloo, Z. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.27856 · Cited by 29 · see citing works
Fernando, R. C., Mazzotti, D. R., de Azevedo, H. F. Z., Sandes, A. F., Rizzatti, E. G., de Oliveira, M. B., Alves, V. L. F., Eugênio, A. I. P., de Carvalho, F., Dalboni, M. A., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-38314-8 · Cited by 28 · see citing works
Self-citationRegulatory T-Cells and Multiple Myeloma: Implications in Tumor Immune Biology and Treatment
Hadjiaggelidou, C., & Katodritou, E. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10194588 · Cited by 28 · see citing works
Kamrani, S., Naseramini, R., Khani, P., Razavi, Z. S., Afkhami, H., Atashzar, M. R., Nasri, F., Alavimanesh, S., Saeidi, F., & Ronaghi, H. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03741-x · Cited by 27 · see citing works
Myeloma cells act as tolerogenic antigen‐presenting cells and induce regulatory T cells in vitro
Frassanito, M. A., Ruggieri, S., Desantis, V., Marzo, L. D., Leone, P., Racanelli, V., Fumarulo, R., Dammacco, F., & Vacca, A. (2014) · European Journal Of Haematology · doi:10.1111/ejh.12481 · Cited by 26 · see citing works
Isazadeh, A., Hajazimian, S., Garshasbi, H., Shadman, B., Baghbanzadeh, A., Chavoshi, R., Taefehshokr, S., Jadid, M. F. S., Hajiasgharzadeh, K., & Baradaran, B. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29905 · Cited by 23 · see citing works
PDCD1 and PDCD1LG1 polymorphisms affect the susceptibility to multiple myeloma
Kasamatsu, T., Awata, M., Ishihara, R., Murakami, Y., Gotoh, N., Matsumoto, M., Sawamura, M., Yokohama, A., Handa, H., Tsukamoto, N., et al. (2019) · Clinical and Experimental Medicine · doi:10.1007/s10238-019-00585-4 · Cited by 22 · see citing works
D'Arena, G. F., Rossi, G., Laurenti, L., Statuto, T., D’Auria, F., Valvano, L., Simeon, V., Giudice, A., Innocenti, I., Feo, V. D., et al. (2016) · Journal of Immunology Research · doi:10.1155/2016/9271469 · Cited by 20 · see citing works
Lenalidomide overcomes the immunosuppression of regulatory CD8+CD28− T-cells
Neuber, B., Dai, J., Waraich, W. A., Awwad, M. H. S., Engelhardt, M., Schmitt, M. W., Medenhoff, S., Witzens‐Harig, M., Ho, A. D., Goldschmidt, H., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21516 · Cited by 18 · see citing works
de Nałęcz, A. K., Ciszak, L., Usnarska‐Zubkiewicz, L., Frydecka, I., Pawlak, E., Szmyrka−Kaczmarek, M., & Kosmaczewska, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179298 · Cited by 18 · see citing works
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The evolution of immune dysfunction in multiple myeloma
Soekojo, C. Y., & Chng, W. J. (2022) · European Journal Of Haematology · doi:10.1111/ejh.13839 · Cited by 16 · see citing works
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Radhakrishnan, V., Golla, U., & Kudva, A. K. (2024) · Life · doi:10.3390/life14040461 · Cited by 18 · see citing works
Leaf, R. K., Cho, H. J., & Avigan, D. (2015) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-015-0283-0 · Cited by 16 · see citing works
Boggio, E. M., Gigliotti, C. L., Moia, R., Scotta, A. M., Crespi, I., Boggione, P., Paoli, L. D., Deambrogi, C., Garzaro, M., Vidali, M., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17968 · Cited by 15 · see citing works
The prognostic and therapeutic potentials of CTLA-4 in hematological malignancies
Sadeghi, M. R., Khodakarami, A., Ahmadi, A., Fathi, M., Navashenaq, J. G., Mohammadi, H., Yousefi, M., Hojjat‐Farsangi, M., Akbari, A. A. M., & Jadidi‐Niaragh, F. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2170781 · Cited by 15 · see citing works
Bauer, D. R., Otter, M., & Chafin, D. R. (2018) · Current Pathobiology Reports · doi:10.1007/s40139-018-0170-1 · Cited by 15 · see citing works
Hervás-Salcedo, R., & Martín-Antonio, B. (2022) · Cancers · doi:10.3390/cancers14153796 · Cited by 13 · see citing works
Wang, L., Shi, M., Sung, A. Y., Yin, C. C., Bai, Y., & Chen, M. (2025) · Seminars in Diagnostic Pathology · doi:10.1016/j.semdp.2025.150916 · Cited by 13 · see citing works
A Unique Role of T Helper 17 Cells in Different Treatment Stages of Multiple Myeloma
Ma, T., Zhang, Y., Zhou, X., Xie, P., & Li, J. (2019) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2019.12.009 · Cited by 12 · see citing works
Checkpoint inhibition in myeloma
Benson, D. M. (2016) · Hematology · doi:10.1182/asheducation-2016.1.528 · Cited by 12 · see citing works
Wilms tumor gent 1 (WT1)-specific adoptive immunotherapy in hematologic diseases
Jiang, Y., Lv, X., Ge, X., Qu, H., Zhang, Q., Lu, K., Lu, Y., Xue, C., Zhang, L., & Wang, X. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107504 · Cited by 11 · see citing works
Tuerxun, N., Wang, J., Qin, Y., Zhao, F., Wang, H., Qu, J., Uddin, M. N., & Jian-ping, H. (2022) · Hematology · doi:10.1080/16078454.2022.2068873 · Cited by 10 · see citing works
Plano, F., Corsale, A. M., Gigliotta, E., Camarda, G. M., Vullo, C., Simone, M. D., Azgomi, M. S., Speciale, M., Carlisi, M., Caccamo, N., et al. (2023) · Hematology Reports · doi:10.3390/hematolrep15010004 · Cited by 9 · see citing works
Selinexor’s Immunomodulatory Impact in Advancing Multiple Myeloma Treatment
Tasbihi, K., & Bruns, H. (2025) · Cells · doi:10.3390/cells14060430 · Cited by 8 · see citing works
Takahashi, S., Minnie, S. A., Ensbey, K. S., Schmidt, C. R., Sekiguchi, T., Legg, S. R. W., Zhang, P., Koyama, M., Olver, S. D., Collinge, A. D., et al. (2024) · Blood · doi:10.1182/blood.2023022000 · Cited by 6 · see citing works
Analysis of peripheral blood T-cell subsets and regulatory T-cells in multiple myeloma patients
Huang, L.-Q., Wang, J., He, K., Jiang, Y., Wei, Z., Huang, D., & Chu, L.-L. (2018) · Cellular and Molecular Biology · doi:10.14715/cmb/2018.64.5.19 · Cited by 5 · see citing works
Kinoshita, R., Ishibashi, M., Handa, H., Sasaki, M., Imai, Y., Tanaka, N., Ito, S., Sunakawa-Kii, M., Kaito, Y., Asayama, T., et al. (2023) · Experimental Hematology · doi:10.1016/j.exphem.2023.01.006 · Cited by 4 · see citing works
Cellular immunity in the era of modern multiple myeloma therapy
Liu, Z., Zhao, X., Shen, H., Liu, X., Xu, X., & Fu, R. (2023) · International Journal of Cancer · doi:10.1002/ijc.34609 · Cited by 5 · see citing works
Inhibitor eradication in refractory acquired hemophilia with lenalidomide
Pfrepper, C., Poenisch, W., Pierer, M., Metze, M., Kaiser, T., & Petros, S. (2019) · Annals of Hematology · doi:10.1007/s00277-019-03620-2 · Cited by 4 · see citing works
Advances in immune microenvironment profiling during multiple myeloma progression and therapy
Bai, J., Nishimura, N., & Kawano, Y. (2025) · International Journal of Hematology · doi:10.1007/s12185-025-04110-0 · Cited by 4 · see citing works
The role of bone marrow microenvironment on CAR‐T efficacy in haematologic malignancies
Gao, D., Hong, F., & He, A. (2023) · Scandinavian Journal of Immunology · doi:10.1111/sji.13273 · Cited by 3 · see citing works
Harnessing the T Cell to Treat Multiple Myeloma: Dawn of a New Therapeutic Paradigm
Keller, A. L., Sherbenou, D. W., Forsberg, P. A., & Mark, T. M. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.925818 · Cited by 3 · see citing works
Ciomber, A., Mitrus, I., Fidyk, W., Smagur, A., Chwieduk, A., Głowala‐Kosińska, M., Czerw, T., Sobczyk‐Kruszelnicka, M., Mendrek, W., Saduś‐Wojciechowska, M., et al. (2016) · Experimental Hematology · doi:10.1016/j.exphem.2016.08.001 · Cited by 3 · see citing works
Bertuglia, G., Cani, L., Larocca, A., Gay, F., & D’Agostino, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415879 · Cited by 3 · see citing works
Kulig, P., Rałowiec, A., Baumert, B., & Machaliński, B. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01728-6 · Cited by 2 · see citing works
Xu, P., Li, Y., Zhuang, X., Yue, L., Ma, Y., Xue, W., Ji, L., Zhan, Y., Ou, Y., Qiao, T., et al. (2024) · Immunologic Research · doi:10.1007/s12026-024-09521-5 · Cited by 2 · see citing works
Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy
Kamali, A. N., Hamedifar, H., Eisenhut, M., & Bautista, J. M. (2024) · Therapeutic Advances in Vaccines and Immunotherapy · doi:10.1177/25151355241288453 · Cited by 2 · see citing works
A study to identify novel biomarkers associated with multiple myeloma
Kalarani, I. B., & Veerabathiran, R. (2023) · Siberian Journal of Oncology · doi:10.21294/1814-4861-2023-22-5-134-144 · Cited by 1 · see citing works
T cell phenotype and clonality changes in myeloma patients with short overall survival
Behsen, A. D., Vandsemb, E. N., Slørdahl, T. S., Dybkær, K., Jakobsen, M. Z., Kashif, M., Lund, J., Luong, V., Olsnes, A. M., Waage, A., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.181096 · Cited by 1 · see citing works
Identification and transformation of novel targets for immunotherapy in multiple myeloma
Wang, Y., Wang, Y., Ma, J., Jing, H., Liu, L., Qiu, L., & Hao, M. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003869 · Cited by 1 · see citing works
Feerick, C. L., Lei, L., Swan, D., Leonard, N. A., Lynch, K., Treacy, O., Ritter, T., Krawczyk, J., O'Dwyer, M. E., & Ryan, A. E. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116222 · Cited by 1 · see citing works
Potential Treatment for Multiple Myeloma: Immune Checkpoint Inhibitors
Wang, J., Tan, J., & Lu, Y. (2021) · International Journal of Immunology · doi:10.11648/j.iji.20210903.14 · Cited by 1 · see citing works
The Role of Immune Checkpoints in Cancer Progression
Prasetya, R. A., & Wulansari, D. D. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.105628 · Cited by 1 · see citing works
Kosmaczewska, A., Masternak, A., Kosciow, K., Ciszak, L., Usnarska‐Zubkiewicz, L., Szteblich, A., Potoczek, S., & Frydecka, I. (2019) · Research Square · doi:10.21203/rs.2.14312/v1 · Cited by 1 · see citing works
Multipl miyelom’da CD4+ regülatör T hücrelerin rolü
Ekinci, D., & Özkan, A. (2017) · Cukurova Medical Journal (Çukurova Üniversitesi Tıp Fakültesi Dergisi) · doi:10.17826/cutf.323972
Refining natural killer cell-based immunotherapy
van Eijl, M. (2018) · doi:10.26481/dis.20181219nm
Checkpoint Blockade in Hematologic Malignancies
Charalambous, A., & Schwarzbich, M. (2022) · Springer eBooks · doi:10.1007/978-3-030-80962-1_178-1
Neuroimmunoregulation of Cancer: The Case for Multiple Myeloma
Aqeel, S. B., James, C. M., Hillengass, J., & Repasky, E. A. (2023) · Springer eBooks · doi:10.1007/978-3-031-32429-1_7
Additional file 1 of Hyperfunction of CD4 CD25 regulatory T cells in de novo acute myeloid leukemia
Wan, Y., Zhang, C., Xu, Y., Wang, M., Rao, Q., Xing, H., Tian, Z. R., Tang, K., Mi, Y., Wang, Y., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12375575
Additional file 3 of Hyperfunction of CD4 CD25 regulatory T cells in de novo acute myeloid leukemia
Wan, Y., Zhang, C., Xu, Y., Wang, M., Rao, Q., Xing, H., Tian, Z., Tang, K., Mi, Y., Wang, Y., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12375587
The Effect of Bone Marrow CD4/CD8 Ratio on Lymphoma Response and Survival: Single Center Experience
Çavdar, V. C., Sönmez, D., Orhan, B., Serin, H., Yokuş, O., & Serin, İ. (2025) · Istanbul Medical Journal · doi:10.4274/imj.galenos.2025.84760
Singer, M., Moloudizargari, M., Sanchez, J. F., & Pichiorri, F. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1642609
Checkpoint Blockade in Hematologic Malignancies
Charalambous, A., & Schwarzbich, M. (2025) · Springer eBooks · doi:10.1007/978-3-032-00765-0_178
Additional file 2 of Hyperfunction of CD4 CD25 regulatory T cells in de novo acute myeloid leukemia
Wan, Y., Zhang, C., Xu, Y., Wang, M., Rao, Q., Xing, H., Tian, Z., Tang, K., Mi, Y., Wang, Y., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12375578
Du, L., Jiang, Y., Zhou, Q., & Xu, F. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1830089
Chen, J., Yu, X., Li, J., Huang, H., Liu, Q., Zhang, D., & Sun, P. (2026) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2026.109247
Bispecific Antibodies and T‐Cell Engagers in Multiple Myeloma
Bhatt, M., Rajkumar, S. V., & Kumar, S. K. (2026) · European Journal Of Haematology · doi:10.1111/ejh.70301
Beyond the M-spike - immunoparesis and multiple myeloma. A narrative review
Mayne, E. S., Worsley, C. M., & Wiggill, T. M. (2026) · Immunology Letters · doi:10.1016/j.imlet.2026.107236
- Authors
- Braga, W. M. T., da Silva, B. R., de Carvalho, A. C., Maekawa, Y. H., Bortoluzzo, A. B., Rizzatti, E. G., Atanackovic, D., & Colleoni, G. W. B.
- Affiliations
- Fleury S.A. (Brazil) (BR)
- Insper (BR)
- University Medical Center Hamburg-Eppendorf (DE)
- Universidade Federal de São Paulo (BR)
- Corresponding author
- Colleoni, Gisele Wally Braga
- ORCID
- Venue
- Cancer Immunology, Immunotherapy
- Published
- 2014-08-07
- Volume
- 63
- Issue
- 11
- Pages
- 1189-1197
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC4209089
- OpenAlex
- W2020191927
- Cited by
- 88
- References
- 39
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 4 · 2023: 9 · 2022: 12 · 2021: 9 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 1
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cancer Immunology Immunotherapy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2010-17668-6, 10/17668-6)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- multiple myeloma, Foxp3, CTLA-4, regulatory T cells, Th17 cells, RORγt, bone marrow microenvironment, immunosuppression, prognostic factors, overall survival, antitumor immunity, monoclonal gammopathy of undetermined significance, solitary plasmacytoma
- MeSH terms
- Adult, Aged, Aged, 80 and over, Bone Marrow, Bone Marrow Cells, Female, Humans, Immunosuppression Therapy, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Plasmacytoma, Biomarkers, Gene Expression Regulation, Neoplastic, Treatment Outcome, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Syndecan-1, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells, CTLA-4 Antigen
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