Back to Search
Start Over
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.
- Source :
-
Frontiers in immunology [Front Immunol] 2020 Nov 06; Vol. 11, pp. 583382. Date of Electronic Publication: 2020 Nov 06 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- 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 <superscript>+</superscript> progenitor exhausted CD8 <superscript>+</superscript> T cells seem to grant the best melanoma prognosis and also efficiently respond to anti-PD-1 immunotherapy, giving rise to a TIM-3 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> PD-1 <superscript>+</superscript> CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br /> (Copyright © 2020 León-Letelier, Castro-Medina, Badillo-Godinez, Tepale-Segura, Huanosta-Murillo, Aguilar-Flores, De León-Rodríguez, Mantilla, Fuentes-Pananá, López-Macías and Bonifaz.)
- Subjects :
- Animals
Bacterial Proteins immunology
Bacterial Proteins pharmacology
CD8-Positive T-Lymphocytes drug effects
Cancer Vaccines pharmacology
Humans
Immune Checkpoint Inhibitors pharmacology
Immunization
Immunologic Memory drug effects
Immunologic Memory immunology
Immunotherapy methods
Lymphocytes, Tumor-Infiltrating drug effects
Lymphocytes, Tumor-Infiltrating immunology
Male
Mice
Mice, Inbred C57BL
Porins pharmacology
Salmonella typhi
Adjuvants, Immunologic pharmacology
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines immunology
Melanoma immunology
Porins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 33240271
- Full Text :
- https://doi.org/10.3389/fimmu.2020.583382