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
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 n...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.583382/full |
| _version_ | 1819008026678394880 |
|---|---|
| author | Ricardo A. León-Letelier Ricardo A. León-Letelier Daniel I. Castro-Medina Oscar Badillo-Godinez Araceli Tepale-Segura Enrique Huanosta-Murillo Cristina Aguilar-Flores Saraí G. De León-Rodríguez Saraí G. De León-Rodríguez Alejandra Mantilla Ezequiel M. Fuentes-Pananá Constantino López-Macías Laura C. Bonifaz |
| author_facet | Ricardo A. León-Letelier Ricardo A. León-Letelier Daniel I. Castro-Medina Oscar Badillo-Godinez Araceli Tepale-Segura Enrique Huanosta-Murillo Cristina Aguilar-Flores Saraí G. De León-Rodríguez Saraí G. De León-Rodríguez Alejandra Mantilla Ezequiel M. Fuentes-Pananá Constantino López-Macías Laura C. Bonifaz |
| author_sort | Ricardo A. León-Letelier |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T00:33:56Z |
| format | Article |
| id | doaj.art-80374f48840a489da5dd0d218ae6c397 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T00:33:56Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-80374f48840a489da5dd0d218ae6c3972022-12-21T19:21:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.583382583382Induction of Progenitor Exhausted Tissue-Resident Memory CD8+ T Cells Upon Salmonella Typhi Porins Adjuvant Immunization Correlates With Melanoma Control and Anti-PD-1 Immunotherapy CooperationRicardo A. León-Letelier0Ricardo A. León-Letelier1Daniel I. Castro-Medina2Oscar Badillo-Godinez3Araceli Tepale-Segura4Enrique Huanosta-Murillo5Cristina Aguilar-Flores6Saraí G. De León-Rodríguez7Saraí G. De León-Rodríguez8Alejandra Mantilla9Ezequiel M. Fuentes-Pananá10Constantino López-Macías11Laura C. Bonifaz12Unidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoPosgrado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, MexicoUnidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoCentro de Investigación Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, MexicoUnidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoUnidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoUnidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoUnidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoPosgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico City, MexicoServicio de Patología, Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoUnidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Mexico City, MexicoUnidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoUnidad de Investigación Médica en Inmunoquímica, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoImmunotherapy 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.583382/fullmelanomaimmunotherapyadjuvanttissue-resident memory T cellsprogenitor exhausted T cellsanti-PD-1 Ab |
| spellingShingle | Ricardo A. León-Letelier Ricardo A. León-Letelier Daniel I. Castro-Medina Oscar Badillo-Godinez Araceli Tepale-Segura Enrique Huanosta-Murillo Cristina Aguilar-Flores Saraí G. De León-Rodríguez Saraí G. De León-Rodríguez Alejandra Mantilla Ezequiel M. Fuentes-Pananá Constantino López-Macías Laura C. Bonifaz 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 Frontiers in Immunology melanoma immunotherapy adjuvant tissue-resident memory T cells progenitor exhausted T cells anti-PD-1 Ab |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | melanoma immunotherapy adjuvant tissue-resident memory T cells progenitor exhausted T cells anti-PD-1 Ab |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.583382/full |
| work_keys_str_mv | AT ricardoaleonletelier inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT ricardoaleonletelier inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT danielicastromedina inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT oscarbadillogodinez inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT aracelitepalesegura inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT enriquehuanostamurillo inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT cristinaaguilarflores inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT saraigdeleonrodriguez inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT saraigdeleonrodriguez inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT alejandramantilla inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT ezequielmfuentespanana inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT constantinolopezmacias inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation AT lauracbonifaz inductionofprogenitorexhaustedtissueresidentmemorycd8tcellsuponsalmonellatyphiporinsadjuvantimmunizationcorrelateswithmelanomacontrolandantipd1immunotherapycooperation |