Exploring the genetic changes caused by vaccine treatment on MC38 tumor tissue
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE279478 | GEO | 2024/10/20
REPOSITORIES: GEO
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Project description:Exploring the genetic changes caused by vaccine treatment on MC38 tumor tissue
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Project description:Introduction: Optimal approaches to induce T-cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T-cell recruitment, and may be induced by IFNgamma. This study tests the hypothesis that intratumoral administration of IFNgamma will induce CXCL9-11, and will induce T-cell recruitment and anti-tumor immune signatures in melanoma metastases. Patients and Methods: Nine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides (12MP) and received IFNgamma intratumorally. Effects on the tumor microenvironment (TME) were evaluated in sequential tumor biopsies. Adverse events (AE; CTCAE v4) were recorded. T-cell responses to vaccination were assessed in peripheral blood (PBMC) by IFNgamma ELIspot assay. Tumor biopsies were evaluated for immune cell infiltration, chemokine protein expression and gene expression. Results: Vaccination and intratumoral administration of IFNgamma were well tolerated. Circulating T-cell responses to vaccine were detected in 6 of 9 patients. IFNgamma increased production of chemokines CXCL10, CXCL11, and CCL5 in patient tumors. Neither vaccination alone nor the addition of IFNgamma promoted immune cell infiltration or induced anti-tumor immune gene signatures. Conclusion: The cancer vaccine did not significantly increase T-cell infiltration of tumors. This study provides intriguing findings highlighting some of the limitations of intratumoral IFNgamma treatment. Although IFNgamma is pivotal in anti-tumor immunity, single intratumoral injection may induce secondary immune regulation that paradoxically limits immune infiltration and effector functions. Therefore, alternate dosing strategies or additional combinatorial treatments may be needed to optimally promote trafficking and retention of T-cells in tumor, which merit further study.
2017-03-01 | GSE79741 | GEO
Project description:Personalized cancer vaccines aim to activate and expand cytotoxic anti-tumor CD8+ T cells to recognize and kill tumor cells. However, the role of CD4+ T cell activation in the clinical benefit of these vaccines is not well defined. We previously established a personalized neoantigen vaccine (PancVAX) for the pancreatic cancer cell line Panc02, which activates tumor-specific CD8+ T cells but required combinatorial checkpoint modulators to achieve therapeutic efficacy. To determine the effects of neoantigen-specific CD4+ T cell activation, we generated a new vaccine (PancVAX2) targeting both MHCI- and MHCII-specific neoantigens. Tumor-bearing mice vaccinated with PancVAX2 had significantly improved control of tumor growth and long-term survival benefit without concurrent administration of checkpoint inhibitors. PancVAX2 significantly enhanced priming and recruitment of neoantigen-specific CD8+ T into the tumor with lower PD1 expression after reactivation compared to the CD8+ vaccine alone. Vaccine-induced neoantigen- specific Th1 CD4+ T cells in the tumor were associated with decreased T regulatory cells (Tregs). Consistent with this, PancVAX2 was associated with more pro-immune myeloid-derived suppressor cells and M1-like macrophages in the tumor demonstrating a less immunosuppressive tumor microenvironment. This study demonstrates the biological importance of prioritizing and including CD4 T cell-specific neoantigens for personalized cancer vaccine modalities.
2023-12-11 | GSE244992 | GEO
Project description:Therapeutic Exosomal Vaccine for Enhanced Cancer Immunotherapy by Mediating Tumor Microenvironment
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Project description:Tumor immunotherapy has been convincingly demonstrated as a feasible approach for treating cancers. Although promising, however, the immunosuppressive tumor microenvironment (TME) has been recognized as a major obstacle in tumor immunotherapy. It is highly desirable to release an immunosuppressive “brake” for improving cancer immunotherapy. Among tumor-infiltrated immune cells, tumor-associated macrophages (TAMs) play an important role in the growth, invasion and metastasis of tumors. The polarization of TAMs (M2) into the M1 type can alleviate the immunosuppression of the TME and enhance the effect of immunotherapy. Inspired by this, we constructed a therapeutic exosomal vaccine from antigen-stimulated M1-type macrophages (M1OVA-Exos). M1OVA-Exos are capable of polarizing TAMs into M1 type through downregulation of the Wnt signaling pathway. Mediating the TME further activates the immune response and inhibits tumor growth and metastasis via the exosomal vaccine. Our study provides a new strategy for the polarization of TAMs, which augments cancer vaccine therapy efficacy.
2022-01-12 | GSE190619 | GEO
Project description:The paper describes a model of antitumor vaccine therapy.
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This model is described in the article:
A Mathematical Model of the Enhancement of Tumor Vaccine Efficacy by Immunotherapy
Shelby Wilson and Doron Levy
Bull Math Biol. 2012 July ; 74(7)
Abstract:
TGF-β is an immunoregulatory protein that contributes to inadequate antitumor immune responses in cancer patients. Recent experimental data suggests that TGF-β inhibition alone, provides few clinical benefits, yet it can significantly amplify the anti-tumor immune response when combined with a tumor vaccine. We develop a mathematical model in order to gain insight into the cooperative interaction between anti-TGF-β and vaccine treatments. The mathematical model follows the dynamics of the tumor size, TGF-β concentration, activated cytotoxic effector cells, and regulatory T cells. Using numerical simulations and stability analysis, we study the following scenarios: a control case of no treatment, anti-TGF-β treatment, vaccine treatment, and combined anti-TGF-β vaccine treatments. We show that our model is capable of capturing the observed experimental results, and hence can be potentially used in designing future experiments involving this approach to immunotherapy.
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2024-09-02 | BIOMD0000000791 | BioModels
Project description:Adoptive cell transfer (ACT) using neoantigen-specific T cells is an effective immunotherapeutic strategy. However, the difficulty in identifying and screening neoantigen-specific T cells limits its widespread application. Here, we prepared neoantigen-reactive T cells (NRTs) after immunization with a tumor lysate-loaded dendritic cell (DC) vaccine (OCDC) for ACT. Our results demonstrated that the OCDC vaccine could induce a neoantigen-specific immune response, and it was feasible to prepare NRTs by loading immunogenic neoantigens onto DCs and coculturing them with spleen lymphocytes from mice immunized with the OCDC vaccine. We then transferred these NRTs back to the LL/2 tumor-bearing mice after OCDC vaccine immunization and found that OCDC vaccine and NRTs adoptive transfer combination treatment could induce a stronger antitumor response. Furthermore, we found that infused NRTs could migrate into the tumor microenvironment to exert antitumor effects. Our research provides a new and convenient method of preparing NRTs for ACT. The clinical translation of this approach has the potential to increase ACT efficacy.
2024-07-05 | GSE271086 | GEO
Project description:Adoptive cell transfer (ACT) using neoantigen-specific T cells is an effective immunotherapeutic strategy. However, the difficulty in identifying and screening neoantigen-specific T cells limits its widespread application. Here, we prepared neoantigen-reactive T cells (NRTs) after immunization with a tumor lysate-loaded dendritic cell (DC) vaccine (OCDC) for ACT. Our results demonstrated that the OCDC vaccine could induce a neoantigen-specific immune response, and it was feasible to prepare NRTs by loading immunogenic neoantigens onto DCs and coculturing them with spleen lymphocytes from mice immunized with the OCDC vaccine. We then transferred these NRTs back to the LL/2 tumor-bearing mice after OCDC vaccine immunization and found that OCDC vaccine and NRTs adoptive transfer combination treatment could induce a stronger antitumor response. Furthermore, we found that infused NRTs could migrate into the tumor microenvironment to exert antitumor effects. Our research provides a new and convenient method of preparing NRTs for ACT. The clinical translation of this approach has the potential to increase ACT efficacy.
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Project description:Purpose:gene discrepancy analysis and signaling pathway of tumor tissues in the PBS, Taraxasterol, DC tumor vaccine and Taraxasterol combined with DC tumor vaccine group
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Project description:Concurrent delivery of immune checkpoint blockade improves tumor microenvironment for vaccine-generated immunity
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