Induction of Progenitor Exhausted Tissue-Resident Memory CD8 + T Cells Upon Salmonella Typhi Porins Adjuvant Immunization Correlates With Melanoma Control and Anti-PD-1 Immunotherapy Cooperation.

Autor:	León-Letelier RA; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.; Posgrado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico., Castro-Medina DI; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico., Badillo-Godinez O; Centro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico., Tepale-Segura A; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico., Huanosta-Murillo E; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico., Aguilar-Flores C; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico., De León-Rodríguez SG; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico City, Mexico., Mantilla A; Servicio de Patología, Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico., Fuentes-Pananá EM; Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Mexico City, Mexico., López-Macías C; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico., Bonifaz LC; Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2020 Nov 06; Vol. 11, pp. 583382. Date of Electronic Publication: 2020 Nov 06 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.583382
Abstrakt:	Immunotherapy has improved the clinical response in melanoma patients, although a relevant percentage of patients still cannot be salvaged. The search for the immune populations that provide the best tumor control and that can be coaxed by immunotherapy strategies is a hot topic in cancer research nowadays. Tumor-infiltrating TCF-1 + progenitor exhausted CD8 + T cells seem to grant the best melanoma prognosis and also efficiently respond to anti-PD-1 immunotherapy, giving rise to a TIM-3 + terminally exhausted population with heightened effector activity. We tested Porins from Salmonella Typhi as a pathogen associated molecular pattern adjuvant of natural or model antigen in prophylactic and therapeutic immunization approaches against murine melanoma. Porins induced protection against melanomas, even upon re-challenging of tumor-free mice. Porins efficiently expanded IFN-γ-producing CD8 + T cells and induced central and effector memory in lymph nodes and tissue-resident (Trm) T cells in the skin and tumors. Porins induced TCF-1 + PD-1 + CD8 + Trm T cells in the tumor stroma and the presence of this population correlated with melanoma growth protection in mice. Porins immunization also cooperated with anti-PD-1 immunotherapy to hamper melanoma growth. Importantly, the potentially protective Trm populations induced by Porins in the murine model were also observed in melanoma patients in which their presence also correlated with disease control. Our data support the use of cancer vaccination to sculpt the tumor stroma with efficient and lasting Trm T cells with effector activities, highlighting the use of Porins as an adjuvant. Furthermore, our data place CD8 + Trm T cells with a progenitor exhausted phenotype as an important population for melanoma control, either independently or in cooperation with anti-PD-1 immunotherapy. (Copyright © 2020 León-Letelier, Castro-Medina, Badillo-Godinez, Tepale-Segura, Huanosta-Murillo, Aguilar-Flores, De León-Rodríguez, Mantilla, Fuentes-Pananá, López-Macías and Bonifaz.)
Databáze:	MEDLINE
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