The Beneficial Effect of IL-12 and IL-18 Transduced Dendritic Cells Stimulated with Tumor Antigens on Generation of an Antitumor Response in a Mouse Colon Carcinoma Model

Mierzejewska, Jagoda; Węgierek-Ciura, Katarzyna; Rossowska, Joanna; Szczygieł, Agnieszka; Anger‐Góra, Natalia; Szermer-Olearnik, Bożena; Geneja, Magdalena; Pajtasz‐Piasecka, Elżbieta

doi:10.1155/2022/7508928

Cited by 7 publications

(6 citation statements)

References 44 publications

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“…IL15 superagonists are promising candidates in preclinical and clinical development for anticancer therapy (49). Although the remarkable antitumor efficacy of IL12 has yet to be replicated in preclinical human models, preclinical studies on the combination of IL12, IL15, and IL18 might represent ideal approaches to generating NK and DCs for cancer therapy (50,51)…”

Section: Discussionmentioning

confidence: 99%

IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines

Do-Thi

Park

et al. 2023

Cancer Research Communications

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Tumor-associated macrophages (TAMs) are involved in tumor progression, metastasis, and immunosuppression. Since TAMs are highly plastic and could alter their phenotypes to pro-inflammatory M1 in response to environmental stimuli, re-educating TAMs has emerged as a promising approach to overcoming the challenges of solid cancer treatment. This study investigated the effect of interleukin (IL)-9 on macrophage M1 polarization and verified its antitumor potential to retrain TAMs and promote chemokine secretion. We demonstrated that IL-9 stimulated macrophage proliferation and polarized them toward the pro-inflammatory M1 phenotype in an IFN-γ-dependent manner. Tumor-localized IL-9 also polarized TAMs toward M1 in vivo and made them release CCL3/4 and CXCL9/10 to recruit antitumor immune cells, including T and NK cells, into the tumor microenvironment. Furthermore, peritoneal treatment with recombinant IL-9 delayed the growth of macrophage-enriched B16F10 melanoma and 4T1 breast cancer in syngeneic mice, although IL-9 treatment did not reduce tumor growth in the absence of macrophage enrichment. These results demonstrate the efficacy of IL-9 in macrophage polarization to trigger antitumor immunity.

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Section: Discussionmentioning

confidence: 99%

IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines

Do-Thi

Park

et al. 2023

Cancer Research Communications

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“…24 hours after placing on the T75 cm 2 flasks, DCs were transduced with LVs with the assumption, that there were 4 viral infectious particles per 1 dendritic cell in the presence of 8 µg/ml polybrene (Sigma−Aldrich; Merck KGaA) [as described by ( 41 )]. 4 hours after the addition of LVs, DCs were stimulated with tumor antigen lysates (TAg, 10% v/v).…”

Section: Methodsmentioning

confidence: 99%

Combined therapy with methotrexate nanoconjugate and dendritic cells with downregulated IL-10R expression modulates the tumor microenvironment and enhances the systemic anti-tumor immune response in MC38 murine colon carcinoma

et al. 2023

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BackgroundUnderstanding the negative impact of the tumor microenvironment on the creation of an effective immune response has contributed to the development of new therapeutic anti-cancer strategies. One such solution is combined therapy consisting of chemotherapeutic administration followed by dendritic cell (DC)-based vaccines. The use of cytostatic leads to the elimination of cancer cells, but can also modulate the tumor milieu. Moreover, great efforts are being made to increase the therapeutic outcome of immunotherapy, e.g. by enhancing the ability of DCs to generate an efficient immune response, even in the presence of immunosuppressive cytokines such as IL-10. The study aimed to determine the effectiveness of combined therapy with chemotherapeutic with immunomodulatory potential – HES-MTX nanoconjugate (composed of methotrexate (MTX) and hydroxyethyl starch (HES)) and DCs with downregulated expression of IL-10 receptor stimulated with tumor antigens (DC/shIL-10R/TAg) applied in MC38 murine colon carcinoma model.MethodsWith the use of lentiviral vectors the DCs with decreased expression of IL-10R were obtained and characterized. During in vivo studies MC38-tumor bearing mice received MTX or HES-MTX nanoconjugate as a sole treatment or combined with DC-based immunotherapy containing unmodified DCs or DCs transduced with shRNA against IL-10R (or control shRNA sequence). Tumor volume was monitored during the experiment. One week after the last injection of DC-based vaccines, tumor nodules and spleens were dissected for ex vivo analysis. The changes in the local and systemic anti-tumor immune response were estimated with the use of flow cytometry and ELISA methods.Results and conclusionsIn vitro studies showed that the downregulation of IL-10R expression in DCs enhances their ability to activate the specific anti-tumor immune response. The use of HES-MTX nanoconjugate and DC/shIL-10R/TAg in the therapy of MC38-tumor bearing mice resulted in the greatest tumor growth inhibition. At the local anti-tumor immune response level a decrease in the infiltration of cells with suppressor activity and an increase in the influx of effector cells into MC38 tumor tissue was observed. These changes were crucial to enhance the effective specific immune response at the systemic level, which was revealed in the greatest cytotoxic activity of spleen cells against MC38 cells.

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“…An engineered decoy-resistant IL-18 restored IL-18 signaling and subsequent anti-tumor activity ( 102 , 103 ). Not only does the cytokine improve anti-tumor activity; IL-18 and IL-12 transduced DCs also showed better recruitment of CD4 and CD8 T cells into tumor microenvironment in mouse colorectal tumor models leading to inhibition of tumor growth ( 104 , 105 )…”

Section: Interleukin 18 Characteristicsmentioning

confidence: 99%

Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment

et al. 2022

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Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine involved in host defense against infections and regulates the innate and acquired immune response. IL-18 is produced by both hematopoietic and non-hematopoietic cells, including monocytes, macrophages, keratinocytes and mesenchymal cell. IL-18 could potentially induce inflammatory and cytotoxic immune cell activities leading to autoimmunity. Its elevated levels have been reported in the blood of patients with some immune-related diseases, including rheumatoid arthritis, systemic lupus erythematosus, type I diabetes mellitus, atopic dermatitis, psoriasis, and inflammatory bowel disease. In the present review, we aimed to summarize the biological properties of IL-18 and its pathological role in different autoimmune diseases. We also reported some monoclonal antibodies and drugs targeting IL-18. Most of these monoclonal antibodies and drugs have only produced partial effectiveness or complete ineffectiveness in vitro, in vivo and human studies. The ineffectiveness of these drugs targeting IL-18 may be largely due to the loophole caused by the involvement of other cytokines and proteins in the signaling pathway of many inflammatory diseases besides the involvement of IL-18. Combination drug therapies, that focus on IL-18 inhibition, in addition to other cytokines, are highly recommended to be considered as an important area of research that needs to be explored.

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The Beneficial Effect of IL-12 and IL-18 Transduced Dendritic Cells Stimulated with Tumor Antigens on Generation of an Antitumor Response in a Mouse Colon Carcinoma Model

Cited by 7 publications

References 44 publications

IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines

IL9 Polarizes Macrophages to M1 and Induces the Infiltration of Antitumor Immune Cells via MIP-1 and CXCR3 Chemokines

Combined therapy with methotrexate nanoconjugate and dendritic cells with downregulated IL-10R expression modulates the tumor microenvironment and enhances the systemic anti-tumor immune response in MC38 murine colon carcinoma

Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment

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