Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination

Llópiz, Diana; Aranda, Fernando; Díaz-Valdés, Nancy; Ruiz, Marta; Infante, Stefany; Belsue, Virginia; Lasarte, Juan José; Sarobe, Pablo

doi:10.1080/2162402x.2015.1075113

Cited by 21 publications

(44 citation statements)

References 39 publications

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“…Although, as previously mentioned, IL-10 can be expressed by different cell subsets, we and others ( 43 , 75 ) have demonstrated that antigen presenting cell-derived IL-10 down-regulates the elicitation of Th1 responses. Indeed, vaccine-dependent induction of IFN-gamma-producing T-cells is greatly enhanced by IL-10 blockade when using adjuvants promoting IL-10 production by DC ( 75 ), which in the case of tumors results in a stronger therapeutic effect ( 43 ). Thus, although different IL-10 sources coexist in the tumor setting, DC-derived IL-10 seems to determine vaccination efficacy.…”

Section: Il-10: An Inhibitory Molecule In Vaccinationmentioning

confidence: 53%

“…Indeed, although there are differences between murine and human studies because of the type of DC subsets and the corresponding TLR repertoire ( 39 ), some stimuli like TLR molecules (TLR2, TLR4, TLR7, or TLR9, among others) strongly induce IL-10 production ( 32 , 40 , 41 ). However, others like TLR3 ligand poly(I:C) or CD40 agonists (CD40L or antiCD40 antibodies) are considered poorer IL-10 inducers, mainly when used alone ( 42 , 43 ). DC receptors responsible for sensing microbial or endogenous inflammatory/danger signals can be grouped according to the mediator molecules and the corresponding signaling pathways used to induce DC activation ( 44 ).…”

Section: Il-10: An Inhibitory Molecule In Vaccinationmentioning

confidence: 99%

“…However, if T-cell priming or generation of an antitumor immune response is needed, as in vaccination, therapeutic benefit would be achieved by IL-10 blockade. Indeed, preclinical data regarding IL-10 blockade has demonstrated an enhancement of vaccine immunogenicity, not only in the cancer setting ( 43 , 71 , 72 ) but also in other models ( 41 , 73 , 74 ). Although, as previously mentioned, IL-10 can be expressed by different cell subsets, we and others ( 43 , 75 ) have demonstrated that antigen presenting cell-derived IL-10 down-regulates the elicitation of Th1 responses.…”

Section: Il-10: An Inhibitory Molecule In Vaccinationmentioning

confidence: 99%

“…Indeed, preclinical data regarding IL-10 blockade has demonstrated an enhancement of vaccine immunogenicity, not only in the cancer setting ( 43 , 71 , 72 ) but also in other models ( 41 , 73 , 74 ). Although, as previously mentioned, IL-10 can be expressed by different cell subsets, we and others ( 43 , 75 ) have demonstrated that antigen presenting cell-derived IL-10 down-regulates the elicitation of Th1 responses. Indeed, vaccine-dependent induction of IFN-gamma-producing T-cells is greatly enhanced by IL-10 blockade when using adjuvants promoting IL-10 production by DC ( 75 ), which in the case of tumors results in a stronger therapeutic effect ( 43 ).…”

Section: Il-10: An Inhibitory Molecule In Vaccinationmentioning

confidence: 99%

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Enhancement of Antitumor Vaccination by Targeting Dendritic Cell-Related IL-10

et al. 2018

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Understanding mechanisms associated to dendritic cell (DC) functions has allowed developing new antitumor therapeutic vaccination strategies. However, these vaccines have demonstrated limited clinical results. Although the low immunogenicity of tumor antigens used and the presence of tumor-associated suppressive factors may in part account for these results, intrinsic vaccine-related factors may also be involved. Vaccines modulate DC functions by inducing activating and inhibitory signals that determine ensuing T cell responses. In this mini review, we focus on IL-10, inhibitory cytokine induced in DC upon vaccination, which defines a suppressive cell subset, discussing its implications as a potential target in combined vaccination immunotherapies.

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Section: Il-10: An Inhibitory Molecule In Vaccinationmentioning

confidence: 53%

Section: Il-10: An Inhibitory Molecule In Vaccinationmentioning

confidence: 99%

Section: Il-10: An Inhibitory Molecule In Vaccinationmentioning

confidence: 99%

Section: Il-10: An Inhibitory Molecule In Vaccinationmentioning

confidence: 99%

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Enhancement of Antitumor Vaccination by Targeting Dendritic Cell-Related IL-10

et al. 2018

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“…Tumour inhibition was also improved in a therapeutic setting by intraperitoneal administration of anti-IL-10 receptor antibodies 14 .…”

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confidence: 99%

Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment

Ni¹,

Wu²,

Liu³

et al. 2020

Preprint

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Development of a vaccine formula that alters the tumour-infiltrating lymphocytes to be more immune active against a tumour is key to the improvement of clinical responses to immunotherapy. Here, we demonstrate that, in conjunction with E7 antigen specific immunotherapy, and IL-10 and PD-1 blockade, intra-tumoral administration of caerin 1.1 and 1.9 peptides further improves the tumour microenvironment (TME) when compared with injection of a control peptide. We used single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity across different cell types within the TME. We show that the injection of caerin 1.1/1.9 increases immune activating macrophages and NK cells, while reducing immunosuppressive macrophages with M2 phenotype, and increased numbers of activated CD8+ T cells with higher populations of memory and effector-memory CD8+ T subsets. Proteomic profiling demonstrated activation of Stat1 modulated apoptosis and production of nitric oxide. Further, computational integration of the proteome with the single cell transcriptome was consistent with deactivation of immune suppressive B cell function following caerin 1.1 and 1.9 treatment.

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Intratumoral injection of caerin 1.1 and 1.9 peptides increases the efficacy of vaccinated TC‐1 tumor‐bearing mice with PD‐1 blockade by modulating macrophage heterogeneity and the activation of CD8⁺ T cells in the tumor microenvironment

Yang

et al. 2021

Clin & Trans Imm

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Objectives Developing a vaccine formula that alters the tumor‐infiltrating lymphocytes to be more immune active against a tumor is key to the improvement of clinical responses to immunotherapy. Here, we demonstrate that, in conjunction with E7 antigen‐specific immunotherapy, and IL‐10 and PD‐1 blockade, intratumoral administration of caerin 1.1/1.9 peptides improves TC‐1 tumor microenvironment (TME) to be more immune active than injection of a control peptide. Methods We compared the survival time of vaccinated TC‐1 tumor‐bearing mice with PD‐1 and IL‐10 blockade, in combination with a further injection of caerin 1.1/1.9 or control peptides. The tumor‐infiltrating haematopoietic cells were examined by flow cytometry. Single‐cell transcriptomics and proteomics were used to quantify changes in cellular activity across different cell types within the TME. Results The injection of caerin 1.1/1.9 increased the efficacy of vaccinated TC‐1 tumor‐bearing mice with anti‐PD‐1 treatment and largely expanded the populations of macrophages and NK cells with higher immune activation level, while reducing immunosuppressive macrophages. More activated CD8 + T cells were induced with higher populations of memory and effector‐memory CD8 + T subsets. Computational integration of the proteome with the single‐cell transcriptome supported activation of Stat1 ‐modulated apoptosis and significant reduction in immune‐suppressive B‐cell function following caerin 1.1 and 1.9 treatment. Conclusions Caerin 1.1/1.9‐containing treatment results in improved antitumor responses. Harnessing the novel candidate genes preferentially enriched in the immune active cell populations may allow further exploration of distinct macrophages, T cells and their functions in TC‐1 tumors.

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Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination

Cited by 21 publications

References 39 publications

Enhancement of Antitumor Vaccination by Targeting Dendritic Cell-Related IL-10

Enhancement of Antitumor Vaccination by Targeting Dendritic Cell-Related IL-10

Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment

Intratumoral injection of caerin 1.1 and 1.9 peptides increases the efficacy of vaccinated TC‐1 tumor‐bearing mice with PD‐1 blockade by modulating macrophage heterogeneity and the activation of CD8⁺ T cells in the tumor microenvironment

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Vaccine-induced but not tumor-derived Interleukin-10 dictates the efficacy of Interleukin-10 blockade in therapeutic vaccination

Cited by 21 publications

References 39 publications

Enhancement of Antitumor Vaccination by Targeting Dendritic Cell-Related IL-10

Enhancement of Antitumor Vaccination by Targeting Dendritic Cell-Related IL-10

Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment

Intratumoral injection of caerin 1.1 and 1.9 peptides increases the efficacy of vaccinated TC‐1 tumor‐bearing mice with PD‐1 blockade by modulating macrophage heterogeneity and the activation of CD8+ T cells in the tumor microenvironment

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Intratumoral injection of caerin 1.1 and 1.9 peptides increases the efficacy of vaccinated TC‐1 tumor‐bearing mice with PD‐1 blockade by modulating macrophage heterogeneity and the activation of CD8⁺ T cells in the tumor microenvironment