Ir al menú de navegación principal Ir al contenido principal Ir al pie de página del sitio

Vol. 14 Núm. 2 (2023)
Vol 14, Núm.2 (2023): Julio-Diciembre

Artículos de investigación / Research papers

Inmunoterapia en Melanoma: Rol de TIGIT y LAG-3 en el microambiente inmune antitumoral

https://doi.org/10.19053/01217488.v14.n2.2023.15041

Publicado 2023-07-19

  • Geidi Catherinne Gaona Neira
    • ,
  • Shanon Daniela Salazar Prieto
    • ,
  • Sandra Milena Rondón Lagos

Geidi Catherinne Gaona Neira
Estudiante de Biología. Grupo de Investigación en Ciencias Biomédicas-UPTC, Escuela de Ciencias Biológicas. Universidad Pedagógica y Tecnológica de Colombia, Tunja, Colombia.

Shanon Daniela Salazar Prieto
Estudiante de Biología. Grupo de Investigación en Ciencias Biomédicas-UPTC, Escuela de Ciencias Biológicas. Universidad Pedagógica y Tecnológica de Colombia, Tunja, Colombia.

Sandra Milena Rondón Lagos
PhD. Grupo de Investigación en Ciencias Biomédicas-UPTC, Escuela de Ciencias Biológicas, Universidad Pedagógica y Tecnológica de Colombia, Tunja, Colombia.

Resumen

El melanoma, es un tumor maligno que surge de los melanocitos. Dada la capacidad de células del melanoma de inactivar linfocitos, la inmunoterapia en melanoma se ha enfocado en emplear inhibidores de puntos de control inmunitario (CPI) para contrarrestar la evasión inmune. El gen de activación de linfocitos 3 (LAG-3) y el receptor inhibitorio con dominios Ig e ITIM (TIGIT) con su ligando específico Nectin-4, son CPIs emergentes que se expresan en células T. En melanoma se evidencia la sobreexpresión de estos receptores inmunitarios, por lo que diferentes ensayos clínicos han desarrollado moléculas inhibitorias que conducen al bloqueo conjunto de LAG-3 y TIGIT/Nectin-4. Dentro de estas moléculas inhibitorias se encuentran PD-1/PD-L1, cuyo uso además de conducir a la reducción de la proliferación y capacidad invasiva del tumor, restaura la actividad de las células T e incrementa la respuesta inmune antitumoral. Sin embargo, la influencia de LAG-3 y TIGIT/Nectin-4 en la actividad inmune antitumoral dentro del microambiente tumoral en melanoma aún no es clara. En esta revisión se describen el rol de los receptores LAG-3 y TIGIT en melanoma, el estado de la monoterapia y la terapia combinada dirigida a estos receptores inmunitarios, la influencia en la respuesta inmune antitumoral y las perspectivas de inmunoterapia dirigidas a LAG-3 y TIGIT/Nectin-4 en melanoma.

Palabras clave

Anticuerpos monoclonales, Terapia antitumoral combinada, punto de control inmunitario, LAG-3, TIGIT, células T

PDF

Biografía del autor/a

Geidi Catherinne Gaona Neira

Soy estudiante de Biología, actualmente estoy en decimo semestre. Algunas de las areas de interés son las ciencias biomédicas y la biotecnología. Actualmente, soy parte del grupo de investigación en Ciencias Biomédicas (GICBUPTC) de la Uptc en el cual estoy analizando STRs para fines de identificación humana en genetica forense en el departamento de Boyacá, además de entrenarme en el uso del software CytoVision para la identificaci´ón y organización de cromosomas humanos y en técnicas de citogenetica como Bandeo GTG y FISH. Además, soy una persona muy dedicada y responsable con gran facilidad de aprendizaje. 

Shanon Daniela Salazar Prieto

Soy estudiante de Biología, actualmente curso decimo semestre, en algunas áreas de mi interés se destacan la genética y la biología molecular siendo estas un componente fuerte dentro de mis estudios universitarios. Hago parte del grupo de investigación en Ciencias Biomédicas de la Uptc en el cual estoy incursionando en el cultivo celular de insectos y el manejo de equipos e instrumentos de laboratorio para el estudio líneas celulares. Es así que me he enfocado en comprender los procesos biológicos desde incógnitas que me surgen a partir de observaciones y vivencias en otros campos de mi vida como el deporte.

Sandra Milena Rondón Lagos

Doctor en Ciencias Biomédicas y Oncología Humana, con amplia experiencia en estudios experimentales sobre cáncer y cultivos celulares. En estos años me he centrado en el estudio de factores pronósticos y predictivos en cáncer de mama, en la evaluación de la respuesta celular a tratamientos oncológicos y en la evaluación de la inestabilidad cromosómica como marcador diagnóstico y pronóstico en cáncer. Los resultados de estos estudios se han presentado en reuniones nacionales e internacionales y se han publicado en revistas internacionales revisadas por pares. Poseo habilidades y facilidades para el diseño, estandarización, ejecución y análisis de experimentos relacionados principalmente con las Ciencias Biomédicas. Soy persistente para lograr los resultados deseados, acepto desafíos, competencia, habilidades técnicas académicas y administrativas. Aprendo rápido y formulo ideas y conceptos. Capacidad en la producción de documentos escritos (propuestas de investigación, redacción de artículos científicos). Facilidad de aprendizaje, dinámica y proactiva.

Citas

  1. W. Guo, H. Wang and C. Li, “Signal pathways of melanoma and targeted therapy. In Signal Transduction and Targeted Therapy”. Nature, vol. 6, pp. 424, 2021. https://doi.org/10.1038/s41392-021-00827-6
  2. H. Sung, et al., “Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries”. CA Cancer J Clin; vol. 71, pp. 209–249, 2021. https://doi.org/10.3322/caac.21660
  3. L. D. Gutiérrez-Castañeda, J. A. Nova y J.D. Tovar-Parra, “Frequency of mutations in BRAF, NRAS, and KIT in different populations and histological subtypes of melanoma: a systemic review: A systemic review”. Melanoma Res; vol. 30, pp. 62–70, 2020. http://dx.doi.org/10.1097/cmr.0000000000000628
  4. M.P. Pistillo, R. Carosio, F. Grillo, V. Fontana, L. Mastracci, A. Morabito, et al., “Phenotypic characterization of tumor CTLA-4 expression in melanoma tissues and its possible role in clinical response to Ipilimumab”. Clin Immunol; vol. 215, pp. 108428, 2020. http://dx.doi.org/10.1016/j.clim.2020.108428
  5. E. Gyukity-Sebestyén, M. Harmati, G. Dobra, I.B. Németh, J. Mihály, Á. Zvara, et al., “Melanoma-derived exosomes induce PD-1 Overexpression and tumor progression via mesenchymal stem cell oncogenic reprogramming”. Front Immunol; vol. 10, pp. 24–59, 2019. http://dx.doi.org/10.3389/fimmu.2019.02459
  6. G. Mattia, R. Puglisi, B. Ascione, W. Malorni, A. Carè y P. Matarrese,“Cell death-based treatments of melanoma:conventional treatments and new therapeutic strategies”. Cell Death Dis; vol. 9, pp. 112, 2018. http://dx.doi.org/10.1038/s41419-017-0059-7
  7. A.M.M. Eggermont, M. Crittenden y J. Wargo, “Combination immunotherapy development in melanoma”. Am Soc Clin Oncol Educ Book; vol. 38, pp. 197–207, 2018. http://dx.doi.org/10.1200/EDBK_201131
  8. R. Gutzmer, D. Stroyakovskiy, H. Gogas, C. Robert, K. Lewis, S. Protsenko, et al., “Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial”. Lancet; vol. 395, pp. 1835–1844, 2020. http://dx.doi.org/10.1016/S0140-6736(20)30934-X
  9. G.V. Long, A. Arance, L. Mortier, P. Lorigan, C. Blank, P. Mohr, et al., “Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006”. Ann Oncol; vol. 33, pp. 204–215, 2022. http://dx.doi.org/10.1016/j.annonc.2021.10.010
  10. C. Robert, G.V. Long, B. Brady, C. Dutriaux, A.M. Di Giacomo, L. Mortier, et al., “Five-year outcomes with nivolumab in patients with wild-type BRAF advanced melanoma”. J Clin Oncol; vol. 38, pp. 3937–3946, 2020. http://dx.doi.org/10.1200/JCO.20.00995
  11. T. Amaral, O. Seeber, E. Mersi, S. Sanchez, I. Thomas, A. Meiwes, et al., “Primary resistance to PD-1-based immunotherapy-A study in 319 patients with stage IV melanoma”. Cancers (Basel); vol. 12, p. 1027, 2020. http://dx.doi.org/10.3390/cancers12041027
  12. A. Relecom, M. Merhi, V. Inchakalody, S. Uddin, D. Rinchai, D. Bedognetti, et al., “Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity”. J Exp Clin Cancer Res; vol. 40, p. 74, 2021. http://dx.doi.org/10.1186/s13046-021-01872-3
  13. J.M. Chauvin, O. Pagliano, J. Fourcade, Z. Sun, H. Wang, C. Sander, et al., “TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients”. J Clin Invest; vol. 125, pp. 2046–2058, 2015. http://dx.doi.org/10.1172/JCI80445
  14. S. Kawashima, T. Inozume, M. Kawazu, T. Ueno, J. Nagasaki, E. Tanji, et al., “TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment”. J Immunother Cancer; vol. 9, p. e003134, 2021. http://dx.doi.org/10.1136/jitc-2021-003134
  15. L.M. Dillon, J. Wojcik, K. Desai, M. Lei, L.Johnson, B. McCune, et al., “Abstract 1625: Distribution and prevalence of LAG-3 expression in samples of melanoma and gastric/gastroesophageal junction cancer”. En: Immunology. Cancer Research, vol. 81, pp. 16–25, 2021. https://doi.org/10.1158/15387445.am2021-1625
  16. H.A. Tawbi, D. Schadendorf, E.J. Lipson, P.A. Ascierto, L. Matamala, E. Castillo Gutiérrez, et al., “Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma”. N Engl J Med; vol. 386, pp. 24–34, 2022. http://dx.doi.org/10.1056/NEJMoa2109970
  17. T. Maruhashi, D. Sugiura, I.M. Okazaki, T. y T. Okazaki, “LAG-3: from molecular functions to clinical applications”. J Immunother Cancer; vol. 8, p. e0010148, 2020.http://dx.doi.org/10.1136/jitc-2020-001014
  18. A.P. Shi, X.Y. Tang, Y.L. Xiong, K.F. Zheng, Y.J. Liu, X.G. Shi, et al., “Immune checkpoint LAG3 and its ligand FGL1 in cancer”. Front Immunol; vol. 12, 2021, p. 785091, 2021. http://dx.doi.org/10.3389/fimmu.2021.785091
  19. F. Xu, J. Liu, D. Liu, B. Liu, M. Wang, Z. Hu, et al., “LSECtin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T-cell responses”. Cancer Res; vol. 74, pp. 3418–3428, 2014.http://dx.doi.org/10.1158/0008-5472.CAN-13-2690
  20. R.N. Amaria, M.A. Postow, M.T. Tetzlaff, M.I. Ross, I.C. Glitza, J.L. McQuade, et al., “Neoadjuvant and adjuvant nivolumab (nivo) with anti-LAG3 antibody relatlimab (rela) for patients (pts) with resectable clinical stage III melanoma”. J Clin Oncol; vol. 39, pp. 9502–9502, 2021. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9502
  21. N. Gestermann, D. Saugy, C. Martignier, L. Tillé, S.A. Fuertes Marraco, M. Zettl, et al., “LAG-3 and PD-1+LAG-3 inhibition promote anti-tumor immune responses in human autologous melanoma/T cell co-cultures”. Oncoimmunology; vol. 9, no. 1, 2020 http://dx.doi.org/10.1080/2162402x.2020.1736792
  22. G.V. Long, F.S. Hodi, E.J. Lipson, D. Schadendorf, P.A. Ascierto, L. Matamala, et al., “Relatlimab and nivolumab versus nivolumab in previously untreated metastatic or unresectable melanoma: Overall survival and response rates from RELATIVITY-047 (CA224-047)”. J Clin Oncol; vol. 40, pp. 360385–360385, 2022. http://dx.doi.org/10.1200/jco.2022.40.36_suppl.360385
  23. R.J. Johnston, L. Comps-Agrar, J. Hackney, X. Yu, M. Huseni, Y. Yang, et al., “The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function”. Cancer Cell; vol. 26, pp. 923–937, 2014.http://dx.doi.org/10.1016/j.ccell.2014.10.018
  24. T.S. Sumida, et al., “Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T Cells”. Nature Immunology, vol. 23, pp. 632–642, 2022. https://doi.org/10.1038/s41590-022-01152-y
  25. D. Bruniquel, et al., “Genomic Organization of the Human LAG-3/CD4 Locus”. Immunogenetics, vol. 47, pp. 96–98, 1997. https://doi.org/10.1038/s41590-022-01152-y
  26. N. Li, et al., “Biochemical Analysis of the Regulatory T Cell Protein Lymphocyte Activation Gene-3 (LAG-3; CD223)”. The Journal of Immunology, vol. 173, pp. 6806–6812, 2004. https://doi.org10.4049/jimmunol.173.11.6806.
  27. B. Huard, et al., “Cellular Expression and Tissue Distribution of the Human LAG-3-Encoded Protein, an MHC Class II Ligand”. Immunogenetics, vol. 39, pp. 213–217, 1994. https://doi.org10.1007/bf00241263.
  28. R. Mastrangeli, et al., “Cloning of Murine LAG-3 by Magnetic Bead Bound Homologous Probes and PCR (Gene-Capture PCR)”. Analytical Biochemistry, vol. 241, pp. 93–102, 1996. https://doi.org10.1006/abio.1996.0382.
  29. J. Petersen and R.Jamie, “Overcoming the LAG3 Phase Problem”. Nature Immunology, vol. 23, pp. 993–995, 2022. https://doi.org10.1038/s41590-022-01239-6.
  30. Q. Ming, et al., “LAG3 Ectodomain Structure Reveals Functional Interfaces for Ligand and Antibody Recognition”. Nature Immunology, vol. 23, pp. 1031–1041, 2022. https://doi.org10.1038/s41590-022-01238-7
  31. C.J. Workman, et al., “Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-3”. The Journal of Immunology, vol. 169, pp. 5392–5395, 2002 https://doi.org10.4049/jimmunol.169.10.5392.
  32. T.K. Maeda, et al., “Atypical Motifs in the Cytoplasmic Region of the Inhibitory Immune Co-Receptor LAG-3 Inhibit T Cell Activation”. The Journal of Biological Chemistry, vol. 294, núm. 15, pp. 6017–6026, 2019. https://doi.org10.1074/jbc.RA119.007455.
  33. Z. Souri, et al., “LAG3 and Its Ligands Show Increased Expression in High-Risk Uveal Melanoma”. Cancers, vol. 13, p. 4445, 2021. https://doi.org10.3390/cancers13174445.
  34. S. Andreae, et al., “MHC Class II Signal Transduction in Human Dendritic Cells Induced by a Natural Ligand, the LAG-3 Protein (CD223)”. Blood, vol. 102, pp. 2130–2137, 2003. https://doi.org10.1182/blood-2003-01-0273.
  35. P. Hemon, et al., “MHC Class II Engagement by Its Ligand LAG-3 (CD223) Contributes to Melanoma Resistance to Apoptosis”. The Journal of Immunology, vol. 186, pp. 5173–5183, 2011. https://doi.org10.4049/jimmunol.1002050.
  36. T. Maruhashi, I. Okazaki, et al., “LAG-3 Inhibits the Activation of CD4+ T Cells That Recognize Stable PMHCII through Its Conformation-Dependent Recognition of PMHCII”. Nature Immunology, vol. 19, pp. 1415–1426, 2018. https://doi.org10.1038/s41590-018-0217-9.
  37. C. Camisaschi, et al., “Alternative Activation of Human Plasmacytoid DCs in Vitro and in Melanoma Lesions: Involvement of LAG-3”. The Journal of Investigative Dermatology, vol. 134, pp. 1893–1902, 2014. https://doi.org10.1038/jid.2014.29.
  38. C. Shan, et al., “Progress of Immune Checkpoint LAG-3 in Immunotherapy”. Oncology Letters, vol. 20, p. 207, 2020. https://doi.org10.3892/ol.2020.1207
  39. T. Maruhashi, S. Daisuke, I. Okazaki, S. Kenji, et al., “Binding of LAG-3 to Stable Peptide-MHC Class II Limits T Cell Function and Suppresses Autoimmunity and Anti-Cancer Immunity”. Immunity, vol. 55, pp. 912-924.e8, 2022. https://doi.org10.1016/j.immuni.2022.03.013.
  40. M.L. Dustin, “The Immunological Synapse”. Cancer Immunology Research, vol. 2, no. 11, 2014, pp. 1023–1033, https://doi.org10.1158/2326-6066.CIR-14-0161
  41. C. Guy, et al., “LAG3 Associates with TCR-CD3 Complexes and Suppresses Signaling by Driving Co-Receptor-Lck Dissociation”. Nature Immunology, vol. 23, pp. 757–767, 2022. https://doi.org10.1038/s41590-022-01176-4.
  42. J. Wang, et al., “Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3”. Cell, vol. 176, pp. 334-347.e12, 2019. https://doi.org10.1016/j.cell.2018.11.010.
  43. T. Kouo, et al., “Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells”. Cancer Immunology Research, vol. 3, no. 4, pp. 412–423, 2015. https://doi.org/10.1158/2326-6066.cir-14-0150
  44. S.O. Bustos, et al., “Galectin-3 Sensitized Melanoma Cell Lines to Vemurafenib (PLX4032) Induced Cell Death through Prevention of Autophagy”. Oncotarget, vol. 9, pp. 14567–14579, 2018. https://doi.org10.18632/oncotarget.24516.
  45. R.R. Braeuer, et al., “Galectin-3 Contributes to Melanoma Growth and Metastasis via Regulation of NFAT1 and Autotaxin”. Cancer Research, vol. 72, pp. 5757–5766, 2012. https://doi.org10.1158/0008-5472.can-12-2424.
  46. C.R. Figueiredo, et al., “Loss of BAP1 Expression Is Associated with an Immunosuppressive Microenvironment in Uveal Melanoma, with Implications for Immunotherapy Development”. The Journal of Pathology, vol. 250, pp. 420–439, 2020. https://doi.org10.1002/path.5384
  47. Z. Souri, P.A. Annemijn, A. Wierenga, Christiaan van Weeghel, et al., “Loss of BAP1 Is Associated with Upregulation of the NFkB Pathway and Increased HLA Class I Expression in Uveal Melanoma”. Cancers, vol. 11, p. 1102, 2019. https://doi.org10.3390/cancers11081102.
  48. A. Fröhlich, et al., “Molecular, Clinicopathological, and Immune Correlates of LAG3 Promoter DNA Methylation in Melanoma”. EBioMedicine, vol. 59, p. 102962, 2020. https://doi.org10.1016/j.ebiom.2020.102962.
  49. C. Camisaschi, C. Chiara, et al., “LAG-3 Expression Defines a Subset of CD4(+) CD25(High) Foxp3(+) Regulatory T Cells That Are Expanded at Tumor Sites”. The Journal of Immunology, vol. 184, pp. 6545–6551, 2010. https://doi.org10.4049/jimmunol.0903879.
  50. A.P. Wiguna y P. Walden, “Role of IL-10 and TGF-β in Melanoma”. Experimental Dermatology, vol. 24, pp. 209–214, 2015. https://doi.org10.1111/exd.12629.
  51. B. Mirlekar, “Tumor Promoting Roles of IL-10, TGF-β, IL-4, and IL-35: Its Implications in Cancer Immunotherapy”. SAGE Open Medicine, vol. 10, p. 20, 2022. https://doi.org10.1177/20503121211069012.
  52. Z. Ge, et al., “TIGIT, the next Step towards Successful Combination Immune Checkpoint Therapy in Cancer”. Frontiers in Immunology, vol. 12, p. 699895, 2021. https://doi.org10.3389/fimmu.2021.699895.
  53. A. Reches, et al., “Nectin4 Is a Novel TIGIT Ligand Which Combines Checkpoint Inhibition and Tumor Specificity”. Journal for Immunotherapy of Cancer, vol. 8, p. e000266, 2020. https://doi.org10.1136/jitc-2019-000266.
  54. F. Arruga, et al., “The Tigit/CD226/CD155 Immunomodulatory Axis Is Deregulated in CLL and Contributes to B-Cell Anergy”. Blood, vol. 138, pp. 3718–3718, 2021. https://doi.org10.1182/blood-2021-150183.
  55. D. Mathew, et al., “LPA5 Is an Inhibitory Receptor That Suppresses CD8 T-Cell Cytotoxic Function via Disruption of Early TCR Signaling”. Frontiers in Immunology, vol. 10, p. 1159, 2019. https://doi.org10.3389/fimmu.2019.01159.
  56. J. Yeo, et al., “TIGIT/CD226 Axis Regulates Anti-Tumor Immunity”. Pharmaceuticals (Basel, Switzerland), vol. 14, p. 200, 2021. https://doi.org10.3390/ph14030200.
  57. X. Liu, et al., “PD-1+ TIGIT+ CD8+ T Cells Are Associated with Pathogenesis and Progression of Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma”. Cancer Immunology, Immunotherapy: CII, vol. 68, pp. 2041–2054, 2019. https://doi.org10.1007/s00262-019-02426-5.
  58. Y. Sun, et al., “Combined Evaluation of the Expression Status of CD155 and TIGIT Plays an Important Role in the Prognosis of LUAD (Lung Adenocarcinoma)”. International Immunopharmacology, vol. 80, p. 106198, 2020. https://doi.org10.1016/j.intimp.2020.106198.
  59. S. Dai, et al., “Intratumoral CXCL13+CD8+T Cell Infiltration Determines Poor Clinical Outcomes and Immunoevasive Contexture in Patients with Clear Cell Renal Cell Carcinoma”. Journal for Immunotherapy of Cancer, vol. 9, p. e001823, 2021. https://doi.org10.1136/jitc-2020-001823.
  60. J. Fourcade, et al., “CD226 Opposes TIGIT to Disrupt Tregs in Melanoma”. JCI Insight, vol. 3, 2013. https://doi.org10.1172/jci.insight.121157.
  61. J. Edwards, et al., “Prevalence and Cellular Distribution of Novel Immune Checkpoint Targets across Longitudinal Specimens in Treatment-Naïve Melanoma Patients: Implications for Clinical Trials”. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, vol. 25, pp. 3247–3258, 2019. https://doi.org10.1158/1078-0432.CCR-18-4011.
  62. C.A. Fuhrman, et al. “Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT and CD226”. The Journal of Immunology, vol. 195, núm. 1, 2015, pp. 145–155, https://doi.org10.4049/jimmunol.1402381.
  63. O. Au, et al., “Abstract 497: Characterization of TIGIT expression using MultiOmyxTMhyperplexed immunofluorescence assay in solid tumors”. Immunology, American Association for Cancer Research, vol. 79, pp. 497-497. 2019. https://doi.org/10.1158/1538-7445.AM2019-497
  64. T. Inozume, et al., “Melanoma Cells Control Antimelanoma CTL Responses via Interaction between TIGIT and CD155 in the Effector Phase”. The Journal of Investigative Dermatology, vol. 136, pp. 255–263, 2016. https://doi.org10.1038/JID.2015.404.
  65. K. Mahnke y H.E. Alexander. “TIGIT-CD155 Interactions in Melanoma: A Novel Co-Inhibitory Pathway with Potential for Clinical Intervention”. The Journal of Investigative Dermatology, vol. 136, pp. 9–11, 2016. https://doi.org10.1016/j.jid.2015.10.048.
  66. J.M. Chauvin, K. Mignane, et al. “IL15 Stimulation with TIGIT Blockade Reverses CD155-Mediated NK-Cell Dysfunction in Melanoma”. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, vol. 26, pp. 5520–5533, 2020. https://doi.org10.1158/1078-0432.CCR-20-0575.
  67. G. Stålhammar, et al., “Expression of Immune Checkpoint Receptors Indoleamine 2,3-Dioxygenase and T Cell Ig and ITIM Domain in Metastatic versus Nonmetastatic Choroidal Melanoma”. Cancer Medicine, vol. 8, pp. 2784–2792, 2019. https://doi.org10.1002/cam4.2167.
  68. Y. Tanaka, et al. “NECTIN4: A Novel Therapeutic Target for Melanoma”. International Journal of Molecular Sciences, vol. 22, p. 976, 2021. https://doi.org10.3390/ijms22020976.
  69. Y. Tanaka, M. Maho, O. Yoshinao, et al., “Nectin Cell Adhesion Molecule 4 (NECTIN4) Expression in Cutaneous Squamous Cell Carcinoma: A New Therapeutic Target?” Biomedicines, vol. 9, p. 355, 2021. https://doi.org10.3390/biomedicines9040355
  70. L. Chocarro, et al. “Clinical Landscape of LAG-3-Targeted Therapy”. Immuno-Oncology Technology, vol. 14, p. 100079, 2022. https://doi.org10.1016/j.iotech.2022.100079.
  71. X. Yu, et al., “Characterization of a Novel Anti-Human Lymphocyte Activation Gene 3 (LAG-3) Antibody for Cancer Immunotherapy”. MAbs, vol. 11, pp. 1139–1148, 2019. https://doi.org10.1080/19420862.2019.1629239.
  72. NIH. Eftilagimod alpha. National Cancer Institute. [online]. 2022. Disponible en: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/eftilagimod
  73. V. Atkinson, et al., “Eftilagimod Alpha, a Soluble Lymphocyte Activation Gene-3 (LAG-3) Protein plus Pembrolizumab in Patients with Metastatic Melanoma”. Journal for Immunotherapy of Cancer, vol. 8, p. e001681, 2020. https://doi.org10.1136/jitc-2020-001681.
  74. W. Zhai, et al., “A Novel Cyclic Peptide Targeting LAG-3 for Cancer Immunotherapy by Activating Antigen-Specific CD8+ T Cell Responses”. Acta Pharmaceutica Sinica. B, vol. 10, pp. 1047–1060, 2020. https://doi.org10.1016/j.apsb.2020.01.005.
  75. X. Bai, et al., “Anti-LAG-3 Antibody LBL-007 in Combination with Toripalimab in Patients with Unresectable or Metastatic Melanoma: A Phase Ⅰ, Open-Label, Multicenter, Dose Escalation/Expansion Study”. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, vol. 40, pp. 9538–9538, 2022. https://doi.org10.1200/jco.2022.40.16_suppl.9538.
  76. H. Jiang, et al., “PD-L1/LAG-3 Bispecific Antibody Enhances Tumor-Specific Immunity”. Oncoimmunology, vol. 10, p. 1943180, 2021. https://doi.org10.1080/2162402X.2021.1943180.
  77. D. Jorgovanovic, et al., “Roles of IFN-γ in Tumor Progression and Regression: A Review”. Biomarker Research, vol. 8, p. 49, 2020. https://doi.org10.1186/s40364-020-00228-x
  78. K. Norville, et al., “A Protease Activatable Interleukin-2 Fusion Protein Engenders Antitumor Immune Responses by Interferon Gamma-Dependent and Interferon Gamma-Independent Mechanisms.” Journal of interferon & cytokine research, vol. 42, no. 7, pp. 316-328, 2022. doi:10.1089/jir.2022.0043
  79. FDA. “Burst Edition: FDA approvals of Opdualag (nivolumab and relatlimab-rmbw) for unresectable or metastatic melanoma, and Keytruda (pembrolizumab) for patients with advanced endometrial carcinoma”. U.S. Food and Drug Administration. 2022. Disponible en: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approvals-opdualag-nivolumab-and-relatlimab-rmbw-unresectable-or
  80. O. Hamid, et al., “Clinical Activity of Fianlimab (REGN3767), a Human Anti-LAG-3 Monoclonal Antibody, Combined with Cemiplimab (Anti-PD-1) in Patients (Pts) with Advanced Melanoma”. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, vol. 39, pp. 9515–9515, 2021. https://doi.org10.1200/jco.2021.39.15_suppl.9515.
  81. C.C. Lin, et al., “387 A Phase II, multicenter study of the safety and efficacy of LAG525 in combination with spartalizumab in patients with advanced malignancies”. Regular and young investigator award abstracts, BMJ Publishing Group Ltd, 2020. https://doi.org/10.1136/jitc-2020-sitc2020.0387
  82. P. Schöffski, et al., “Phase I/II Study of the LAG-3 Inhibitor Ieramilimab (LAG525) ± Anti-PD-1 Spartalizumab (PDR001) in Patients with Advanced Malignancies”. Journal for Immunotherapy of Cancer, vol. 10, p. e003776, 2022. https://doi.org10.1136/jitc-2021-003776.
  83. E. Sung, et al., “LAG-3xPD-L1 Bispecific Antibody Potentiates Antitumor Responses of T Cells through Dendritic Cell Activation”. Molecular Therapy: The Journal of the American Society of Gene Therapy, vol. 30, pp. 2800–2816, 2022. https://doi.org10.1016/j.ymthe.2022.05.003.
  84. F. Dimitriou, et al., “Double Trouble: Immunotherapy Doublets in Melanoma-Approved and Novel Combinations to Optimize Treatment in Advanced Melanoma”. American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Meeting, vol. 42, pp. 1–22, 2022. https://doi.org10.1200/EDBK_351123
  85. F. A. Van den Mooter, et al. “Abstract CT118: Preliminary data from Phase I first-in-human study of EOS884448, a novel potent anti-TIGIT antibody, monotherapy shows favorable tolerability profile and early signsof clinical activity in immune-resistant advanced cancers”. Clinical Trials, American Association for Cancer Research, vol. 81, p. 118, 2021. https://doi.org/10.1158/1538-7445.am2021-ct118.
  86. D. Niebel, et al. “DNA Methylation Regulates TIGIT Expression within the Melanoma Microenvironment, Is Prognostic for Overall Survival, and Predicts Progression-Free Survival in Patients Treated with Anti-PD-1 Immunotherapy”. Clinical Epigenetics, vol. 14, p. 50, 2022. https://doi.org10.1186/s13148-022-01270-2.
  87. S. Merck y L. Dohme. Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/KEYMAKER-U02). 2021a. ClinicalTrials.gov Identifier: NCT04305041
  88. S. Merck y L. Dohme. Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02). 2021b. ClinicalTrials.gov Identifier: NCT04305054
  89. S. Merck y L. Dohme. Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02). 2021c. ClinicalTrials.gov Identifier: NCT04303169
  90. D. Diwakar. Zimberelimab (AB122) With TIGIT Inhibitor Domvanalimab (AB154) in PD-1 Relapsed/Refractory Melanoma. 2022. ClinicalTrials.gov Identifier: NCT05130177
  91. iTeos Belgium SA. Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors (TIG-006). 2021. ClinicalTrials.gov Identifier: NCT05060432
  92. M. Moussa, et al., “Profile of Enfortumab Vedotin in the Treatment of Urothelial Carcinoma: The Evidence to Date”. Drug Design, Development and Therapy, vol. 15, pp. 453–462, 2021. https://doi.org10.2147/DDDT.S240854.
  93. E. Challita, M. Pia, et al., “Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models”. Cancer Research, vol. 76, pp. 3003–3013, 2016. https://doi.org10.1158/0008-5472.CAN-15-1313
  94. J. Bedke and M. Moritz. “Re: Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma”. European Urology, vol. 80, pp. 257–258, 2021. https://doi.org10.1016/j.eururo.2021.04.007.
  95. A.C. Anderson, et al., “Lag-3, Tim-3, and TIGIT: Co-Inhibitory Receptors with Specialized Functions in Immune Regulation”. Immunity, vol. 44, pp. 989–1004, 2016. https://doi.org10.1016/j.immuni.2016.05.001.
  96. H. Harjunpää y C. Guillerey. “TIGIT as an Emerging Immune Checkpoint”. Clinical and Experimental Immunology, vol. 200, pp. 108–119, 2020. https://doi.org10.1111/cei.13407.
  97. B.R. Burton, et al., “Sequential Transcriptional Changes Dictate Safe and Effective Antigen-Specific Immunotherapy”. Nature Communications, vol. 5, 2014. https://doi.org10.1038/ncomms5741
  98. W.J. Lee, et al., “Expression of Lymphocyte-Activating Gene 3 and T-Cell Immunoreceptor with Immunoglobulin and ITIM Domains in Cutaneous Melanoma and Their Correlation with Programmed Cell Death 1 Expression in Tumor-Infiltrating Lymphocytes”. Journal of the American Academy of Dermatology, vol. 81, pp. 219–227, 2019. https://doi.org10.1016/j.jaad.2019.03.012
  99. C.E. Rudd, et al., “Small Molecule Inhibition of GSK-3 Specifically Inhibits the Transcription of Inhibitory Co-Receptor LAG-3 for Enhanced Anti-Tumor Immunity”. Cell Reports, vol. 30, pp. 2075-2082.e4, 2020. https://doi.org10.1016/j.celrep.2020.01.076.
  100. G. Shaw, et al., “Elraglusib (9-ING-41), a selective small molecule inhibitor of Glycogen Synthase Kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3, and enhances CD8+ T cell cytolytic killing of melanoma cells”. Research Square, 2022, https://doi.org10.21203/rs.3.rs-1629579/v1.

Descargas

Los datos de descargas todavía no están disponibles.

Artículos similares

1 2 > >> 

También puede {advancedSearchLink} para este artículo.