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Therapeutic exosomal vaccine for enhanced cancer immunotherapy by mediating tumor microenvironment.

ABSTRACT: Tumor immunotherapy has been convincingly demonstrated as a feasible approach for treating cancers. Although promising, 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 (M1_OVA-Exos). M1_OVA-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.

SUBMITTER: Lv F

PROVIDER: S-EPMC8724970 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Therapeutic Exosomal Vaccine for Enhanced Cancer Immunotherapy by Mediating Tumor Microenvironment

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

Therapeutic Exosomal Vaccine for Enhanced Cancer Immunotherapy by Mediating Tumor Microenvironment

Project description:Therapeutic Exosomal Vaccine for Enhanced Cancer Immunotherapy by Mediating Tumor Microenvironment

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| S-EPMC10494322 | biostudies-literature

Exosomal miRNAs in tumor microenvironment.

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| S-EPMC7164281 | biostudies-literature

Immunomodulatory Prodrug Micelles Imitate Mild Heat Effects to Reshape Tumor Microenvironment for Enhanced Cancer Immunotherapy.

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| S-EPMC10883120 | biostudies-literature

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Project description:Oral cancer is one of the most common malignant tumors of the head and neck, not only affects the appearance, but also affects eating and even endangers life. The clinical treatments of oral cancer mainly include surgery, radiotherapy, and chemotherapy. However, unsatisfactory therapeutic effect and toxic side effects are still the main problems in clinical treatment. Tumor microenvironment (TME) is not only closely related to the occurrence, growth, and metastasis of tumor but also works in the diagnosis, prevention, and treatment of tumor and prognosis. Future studies should continue to investigate the relationship of TME and oral cancer therapy. This purpose of this review was to analyze the characteristics of oral cancer microenvironment, summarize the traditional oral cancer therapy and immunotherapy strategies, and finally prospect the development prospects of oral cancer immunotherapy. Immunotherapy targeting tumor microenvironment is expected to provide a new strategy for clinical treatment of oral cancer.

| S-EPMC9547678 | biostudies-literature

Tumor microenvironment-responsive spherical nucleic acid nanoparticles for enhanced chemo-immunotherapy.

Project description:Certain chemotherapeutics can induce tumor cells' immunogenic cell death (ICD), release tumor antigens, and thereby trigger personalized antitumor immune responses. Co-delivery of adjuvants using nanocarriers could amplify the ICD-induced tumor-specific immunity achieving a synergistic chemo-immunotherapeutic effect. However, complicated preparation, low drug loading efficiency, and potential carrier-associated toxicity are the major challenges that limited its clinical applications. Herein, a carrier-free core-shell nanoparticle (MPLA-CpG-sMMP9-DOX, MCMD NPs) was constructed by facile self-assembly of spherical nucleic acids (SNA) with two adjuvants of CpG ODN and monophosphoryl lipid A (MPLA) as a core and doxorubicin (DOX) radially around the dual-adjuvants SNA as a shell. The results demonstrated that MCMD NPs could enhance drugs accumulation in tumors, and release DOX upon enzymatic degradation of matrix metalloproteinase-9 (MMP-9) peptide in the tumor microenvironment (TME), which enhanced the direct-killing effect of DOX on tumor cells. The core of MPLA-CpG SNA efficiently boosted the ICD-induced antitumor immune response to further attack tumor cells. Thus, MCMD NPs achieved a synergistic therapeutic effect of chemo-immunotherapy with reduced off-target toxicity. This study provided an efficient strategy for the development of a carrier-free nano-delivery system for enhanced cancer chemo-immunotherapy.

| S-EPMC10214549 | biostudies-literature

Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.

Project description:BackgroundThe FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).MethodsRNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.ResultsTranscriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%; P = .0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8 + cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice.ConclusionsThis is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy.

| S-EPMC11376453 | biostudies-literature

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Project description:Chemokines are a large family of small chemotactic cytokines that coordinates immune cell trafficking. In cancer, they have a pivotal role in the migration pattern of immune cells into the tumor, thereby shaping the tumor microenvironment immune profile, often towards a pro-tumorigenic state. Furthermore, chemokines can directly target non-immune cells in the tumor microenvironment, including cancer, stromal and vascular endothelial cells. As such, chemokines participate in several cancer development processes such as angiogenesis, metastasis, cancer cell proliferation, stemness and invasiveness, and are therefore key determinants of disease progression, with a strong influence in patient prognosis and response to therapy. Due to their multifaceted role in the tumor immune response and tumor biology, the chemokine network has emerged as a potential immunotherapy target. Under the present review, we provide a general overview of chemokine effects on several tumoral processes, as well as a description of the currently available chemokine-directed therapies, highlighting their potential both as monotherapy or in combination with standard chemotherapy or other immunotherapies. Finally, we discuss the most critical challenges and prospects of developing targeted chemokines as therapeutic options.

| S-EPMC8464715 | biostudies-literature

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| S-EPMC8489668 | biostudies-literature

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