Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases
Caloric restriction mimetics (CRMs), compounds that mimic the biochemical effects of nutrient deprivation, administered via systemic route promote antitumor effects through the induction of autophagy and the modulation of the immune microenvironment; however, collateral effects due to metabolic chan...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/2015892 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849685363491078144 |
|---|---|
| author | Valentino Le Noci Michele Sommariva Francesca Bianchi Tiziana Triulzi Elda Tagliabue Andrea Balsari Lucia Sfondrini |
| author_facet | Valentino Le Noci Michele Sommariva Francesca Bianchi Tiziana Triulzi Elda Tagliabue Andrea Balsari Lucia Sfondrini |
| author_sort | Valentino Le Noci |
| collection | DOAJ |
| description | Caloric restriction mimetics (CRMs), compounds that mimic the biochemical effects of nutrient deprivation, administered via systemic route promote antitumor effects through the induction of autophagy and the modulation of the immune microenvironment; however, collateral effects due to metabolic changes and the possible weight loss might potentially limit their administration at long term. Here, we investigated in mice local administration of CRMs via aerosol to reduce metastasis implantation in the lung, whose physiologic immunosuppressive status favors tumor growth. Hydroxycitrate, spermidine, and alpha-lipoic acid, CRMs that target different metabolic enzymes, administered by aerosol, strongly reduced implantation of intravenously injected B16 melanoma cells without overt signs of toxicity, such as weight loss and changes in lung structure. Cytofluorimetric analysis of lung immune infiltrates revealed a significant increase of alveolar macrophages and CD103+ dendritic cells in mice treated with CRMs that paralleled an increased recruitment and activation of both CD3 T lymphocytes and NK cells. These effects were associated with the upregulation of genes related to M1 phenotype, as IL-12 and STAT-1, and to the decrease of M2 genes, as IL-10 and STAT-6, in adherent fraction of lung immune infiltrate, as revealed by real-time PCR analysis. Thus, in this proof-of-principle study, we highlight the antitumor effect of CRM aerosol delivery as a new and noninvasive therapeutic approach to locally modulate immunosurveillance at the tumor site in the lung. |
| format | Article |
| id | doaj-art-c3f0bf644325450187014c0f53c3b73a |
| institution | DOAJ |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-c3f0bf644325450187014c0f53c3b73a2025-08-20T03:23:11ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/20158922015892Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung MetastasesValentino Le Noci0Michele Sommariva1Francesca Bianchi2Tiziana Triulzi3Elda Tagliabue4Andrea Balsari5Lucia Sfondrini6Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, ItalyDipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan 20133, ItalyMolecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, ItalyMolecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, ItalyMolecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, ItalyMolecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, ItalyDipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan 20133, ItalyCaloric restriction mimetics (CRMs), compounds that mimic the biochemical effects of nutrient deprivation, administered via systemic route promote antitumor effects through the induction of autophagy and the modulation of the immune microenvironment; however, collateral effects due to metabolic changes and the possible weight loss might potentially limit their administration at long term. Here, we investigated in mice local administration of CRMs via aerosol to reduce metastasis implantation in the lung, whose physiologic immunosuppressive status favors tumor growth. Hydroxycitrate, spermidine, and alpha-lipoic acid, CRMs that target different metabolic enzymes, administered by aerosol, strongly reduced implantation of intravenously injected B16 melanoma cells without overt signs of toxicity, such as weight loss and changes in lung structure. Cytofluorimetric analysis of lung immune infiltrates revealed a significant increase of alveolar macrophages and CD103+ dendritic cells in mice treated with CRMs that paralleled an increased recruitment and activation of both CD3 T lymphocytes and NK cells. These effects were associated with the upregulation of genes related to M1 phenotype, as IL-12 and STAT-1, and to the decrease of M2 genes, as IL-10 and STAT-6, in adherent fraction of lung immune infiltrate, as revealed by real-time PCR analysis. Thus, in this proof-of-principle study, we highlight the antitumor effect of CRM aerosol delivery as a new and noninvasive therapeutic approach to locally modulate immunosurveillance at the tumor site in the lung.http://dx.doi.org/10.1155/2019/2015892 |
| spellingShingle | Valentino Le Noci Michele Sommariva Francesca Bianchi Tiziana Triulzi Elda Tagliabue Andrea Balsari Lucia Sfondrini Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases Journal of Immunology Research |
| title | Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases |
| title_full | Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases |
| title_fullStr | Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases |
| title_full_unstemmed | Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases |
| title_short | Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases |
| title_sort | local administration of caloric restriction mimetics to promote the immune control of lung metastases |
| url | http://dx.doi.org/10.1155/2019/2015892 |
| work_keys_str_mv | AT valentinolenoci localadministrationofcaloricrestrictionmimeticstopromotetheimmunecontroloflungmetastases AT michelesommariva localadministrationofcaloricrestrictionmimeticstopromotetheimmunecontroloflungmetastases AT francescabianchi localadministrationofcaloricrestrictionmimeticstopromotetheimmunecontroloflungmetastases AT tizianatriulzi localadministrationofcaloricrestrictionmimeticstopromotetheimmunecontroloflungmetastases AT eldatagliabue localadministrationofcaloricrestrictionmimeticstopromotetheimmunecontroloflungmetastases AT andreabalsari localadministrationofcaloricrestrictionmimeticstopromotetheimmunecontroloflungmetastases AT luciasfondrini localadministrationofcaloricrestrictionmimeticstopromotetheimmunecontroloflungmetastases |