Immunotherapy in Melanoma: Role of TIGIT and LAG-3 on the antitumor immune microenvironment

Abstract

Melanoma, is a malignant tumor arising from melanocytes. Given the ability of melanoma cells to inactivate lymphocytes, immunotherapy in melanoma has focused on using immune checkpoint inhibitors (ICIs) to counteract immune evasion. The lymphocyte activation gene 3 (LAG-3) and the inhibitory receptor with Ig and ITIM domains (TIGIT) with its specific ligand Nectin-4 are emerging IPCs that are expressed in T cells. Overexpression of these immunological receptors is evident in melanoma, whereby different clinical trials have developed inhibitory molecules (as proven-drugs) that leading to the joint blockage of LAG-3 and TGIT/Nectin-4. Among these inhibitory molecules are PD-1/PD-L1, whose use, in addition to leading to the reduction of tumor proliferation and invasiveness, restores the activity of T cells and increases the antitumor immune response. However, the influence of LAG-3 and TIGIT/Nectin-4 on antitumor immune activity within the tumor microenvironment in melanoma remains unclear. This review describes the role of LAG-3 and TIGIT receptors in melanoma, the status of monotherapy and combination therapy targeting these immune receptors, the influence on the antitumor immune response, and the prospects for LAG-3 targeting immunotherapy. and TIGIT/Nectin-4 in melanoma.

Keywords

Monoclonal antibodies, T cells, LAG-3, immune checkpoint, combined antitumor therapy, TIGIT

Author Biography

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.

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