scholarly journals Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling

2020 ◽  
Vol 217 (5) ◽  
Author(s):  
Yaoyao Shi ◽  
Wenxin Zheng ◽  
Kaiting Yang ◽  
Katharine G. Harris ◽  
Kaiyuan Ni ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Intestinal Microbiota ◽  
Local Delivery ◽  
Host Immunity ◽  
Tumor Tissues ◽  
Gut Immunity

Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 immunotherapy on tumor tissues through the capacity to accumulate within the tumor microenvironment. Systemic administration of Bifidobacterium leads to its accumulation within the tumor and converts the nonresponder mice into responders to anti-CD47 immunotherapy in a stimulator of interferon genes (STING)– and interferon-dependent fashion. Local delivery of Bifidobacterium potently stimulates STING signaling and increases cross-priming of dendritic cells after anti-CD47 treatment. Our study identifies the mechanism by which gut microbiota preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling.

Tumor Microenvironment-Triggered In-Situ Cancer Vaccines with Dual Immunogenic Cell Death Inductions for Elevated Antitumor and Antimetastatic Therapy

Nanoscale ◽  
2021 ◽  
Author(s):  
Jun Lin ◽  
Binbin Ding ◽  
Pan Zheng ◽  
Dong Li ◽  
Meifang Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Cancer Vaccines ◽  
High Specificity ◽  
The Body ◽  
Immunogenic Cell Death ◽  
Specific Antigens

Cancer vaccine is to make tumor-specific antigens into vaccines, which then are injected back into the body to activate immune responses for cancer immunotherapy. Despite the high specificity and therapeutic...

scholarly journals Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment in a murine papillomavirus tumor model

2020 ◽  
Author(s):  
mohsen Keshavarz ◽  
Mir Saeed Ebrahimzadeh ◽  
Seyed Mohammad Miri ◽  
Hassan Dianat-Moghadam ◽  
Seyedeh Sara Ghorbanhosseini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Newcastle Disease Virus ◽  
Cancer Immunotherapy ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Caspase 3

Abstract Background: Cervical cancer is the most common human papillomavirus (HPV)-related cancer caused by persistent genital high-risk HPV infection. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor.Methods: For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME).Results: our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 3 and 9) and increased infiltration of tumor microenvironment with CD11b+myeloid and Gr1+MDSCs cells.Conclusions: Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and MDSCs expansion in the tumor microenvironment.

The impacts of natural polysaccharides on intestinal microbiota and immune responses – a review

2019 ◽  
Vol 10 (5) ◽  
pp. 2290-2312 ◽  
Author(s):  
Chao Tang ◽  
Ruoxi Ding ◽  
Jian Sun ◽  
Jun Liu ◽  
Juan Kan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Intestinal Microbiota ◽  
Comprehensive Review

This paper presents a comprehensive review of the impacts of natural polysaccharides on gut microbiota and immune responses as well as their interactions.

scholarly journals What We Know So Far about the Metabolite-Mediated Microbiota-Intestinal Immunity Dialogue and How to Hear the Sound of This Crosstalk

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 406
Author(s):  
Clément Caffaratti ◽  
Caroline Plazy ◽  
Geoffroy Mery ◽  
Abdoul-Razak Tidjani ◽  
Federica Fiorini ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Immune Cells ◽  
Causal Effect ◽  
Host Immunity ◽  
Intestinal Immunity ◽  
Host Health ◽  
Membrane Bound ◽  
Insight Into

Trillions of microorganisms, termed the “microbiota”, reside in the mammalian gastrointestinal tract, and collectively participate in regulating the host phenotype. It is now clear that the gut microbiota, metabolites, and intestinal immune function are correlated, and that alterations of the complex and dynamic host-microbiota interactions can have deep consequences for host health. However, the mechanisms by which the immune system regulates the microbiota and by which the microbiota shapes host immunity are still not fully understood. This article discusses the contribution of metabolites in the crosstalk between gut microbiota and immune cells. The identification of key metabolites having a causal effect on immune responses and of the mechanisms involved can contribute to a deeper insight into host-microorganism relationships. This will allow a better understanding of the correlation between dysbiosis, microbial-based dysmetabolism, and pathogenesis, thus creating opportunities to develop microbiota-based therapeutics to improve human health. In particular, we systematically review the role of soluble and membrane-bound microbial metabolites in modulating host immunity in the gut, and of immune cells-derived metabolites affecting the microbiota, while discussing evidence of the bidirectional impact of this crosstalk. Furthermore, we discuss the potential strategies to hear the sound of such metabolite-mediated crosstalk.

scholarly journals Dendritic Cells The Tumor Microenvironment and the Challenges for an Effective Antitumor Vaccination

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Fabian Benencia ◽  
Leslee Sprague ◽  
John McGinty ◽  
Michelle Pate ◽  
Maria Muccioli
Keyword(s):  
Clinical Trials ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Potential ◽  
Human Cancer ◽  
Dc Vaccines ◽  
Tumor Clearance ◽  
Antigen Presenting

Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic-cell- (DC-) based vaccines on cancer patients, and recently the first DC-based vaccine for human cancer was approved by the FDA. Herewith, we describe the general characteristics of DCs and different strategies to generate effective antitumor DC vaccines. In recent years, the relevance of the tumor microenvironment in the progression of cancer has been highlighted. It has been shown that the tumor microenvironment is capable of inactivating various components of the immune system responsible for tumor clearance. In particular, the effect of the tumor microenvironment on antigen-presenting cells, such as DCs, does not only render these immune cells unable to induce specific immune responses, but also turns them into promoters of tumor growth. We also describe strategies likely to increase the efficacy of DC vaccines by reprogramming the immunosuppressive nature of the tumor microenvironment.

scholarly journals Oncolytic Newcastle disease virus delivered by Mesenchymal stem cells-engineered system enhances the therapeutic effects altering tumor microenvironment

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Mohsen Keshavarz ◽  
Mir Saeed Ebrahimzadeh ◽  
Seyed Mohammad Miri ◽  
Hassan Dianat-Moghadam ◽  
Seyedeh Sara Ghorbanhosseini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Newcastle Disease Virus ◽  
Cancer Immunotherapy ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Therapeutic Effects

Abstract Background Human papillomavirus (HPV)-associated malignancy remain a main cause of cancer in men and women. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. Here, we report Mesenchymal stem cells (MSCs) as a carrier for the delivery of oncolytic Newcastle disease virus (NDV) for the treatment of HPV-associated tumor. Methods For this purpose, MSCs obtained from the bone marrow of C57BL mice, then cultured and characterized subsequently by the flow cytometry analysis for the presence of cell surface markers. In this study, we sought out to determine the impacts of MSCs loaded with oncolytic NDV on splenic T cell and cytokine immune responses, caspase-3 and -9 expression, and myeloid and myeloid-derived suppressor cells (MDSCs) by histological and immunohistochemical studies in the tumor microenvironment (TME). Results Our findings proved that MSCs possess both migratory capacity and tumor tropism toward transplanted tumor tissue after peritumoral administration. Tumor therapy experiments indicated that oncolytic NDV delivered by MSCs-engineered system significantly reduces tumor growth, which is associated with the enhancement of E7-specific lymphocyte proliferation, CD8+ T cell cytolysis responses, and splenic IFN-γ, IL-4 and IL-12 responses compared with control groups. Moreover, the treatment upregulated the concentration of apoptotic proteins (caspase 9) and increased infiltration of tumor microenvironment with CD11b + myeloid and Gr1 + MDSCs cells. Conclusions Our data suggest MSCs carrying oncolytic NDV as a potentially effective strategy for cancer immunotherapy through inducing splenic Th1 immune responses and apoptosis in the tumor microenvironment.

scholarly journals Combined Effects of Myeloid Cells in the Neuroblastoma Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1743
Author(s):  
Jennifer Frosch ◽  
Ilia Leontari ◽  
John Anderson
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cellular Therapy ◽  
Myeloid Cells ◽  
Host Immunity ◽  
Nutrient Depletion ◽  
Car T Cells ◽  
Neuroblastoma Tumor ◽  
Car T ◽  
Cellular Components

Despite multimodal treatment, survival chances for high-risk neuroblastoma patients remain poor. Immunotherapeutic approaches focusing on the activation and/or modification of host immunity for eliminating tumor cells, such as chimeric antigen receptor (CAR) T cells, are currently in development, however clinical trials have failed to reproduce the preclinical results. The tumor microenvironment is emerging as a major contributor to immune suppression and tumor evasion in solid cancers and thus has to be overcome for therapies relying on a functional immune response. Among the cellular components of the neuroblastoma tumor microenvironment, suppressive myeloid cells have been described as key players in inhibition of antitumor immune responses and have been shown to positively correlate with more aggressive disease, resistance to treatments, and overall poor prognosis. This review article summarizes how neuroblastoma-driven inflammation induces suppressive myeloid cells in the tumor microenvironment and how they in turn sustain the tumor niche through suppressor functions, such as nutrient depletion and generation of oxidative stress. Numerous preclinical studies have suggested a range of drug and cellular therapy approaches to overcome myeloid-derived suppression in neuroblastoma that warrant evaluation in future clinical studies.

scholarly journals Recent development and applications of nanomaterials for cancer immunotherapy

2020 ◽  
Vol 9 (1) ◽  
pp. 367-384 ◽  
Author(s):  
Yao Huang ◽  
Jinhua Zeng
Keyword(s):  
Immune System ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Surface Chemistry ◽  
Specific Surface ◽  
Cancer Immunotherapy ◽  
Cancer Therapies ◽  
Artificial Antigen ◽  
Antigen Presenting ◽  
Fight Against Cancer

AbstractImmunotherapy, which utilizes the patient’s own immune system to fight against cancer, further results in durable antitumor responses and reduces metastasis and recurrence, has become one of the most effective and important cancer therapies along with surgery, radiotherapy, and chemotherapy. Nanomaterials with the advantages of large specific surface, delivery function, and controllable surface chemistry are used to deliver antigens or adjuvants, or both, help to boost immune responses with the imaging function or just act as adjuvants themselves and modulate tumor microenvironment (TME). In this review, recent development and applications of nanomaterials for cancer immunotherapy including delivery systems based on nanomaterials, uniting imaging, self-adjuvants, targeting functions, artificial antigen presenting cells, and TME modulation are focused and discussed.

Influenza mimetic protein–polymer nanoparticles as antigen delivery vehicles to dendritic cells for cancer immunotherapy

Nanoscale ◽  
2019 ◽  
Vol 11 (29) ◽  
pp. 13878-13884 ◽  
Author(s):  
Chaeyeon Lee ◽  
Leeja Jose ◽  
KyuHwan Shim ◽  
Seong Soo A. An ◽  
Sunah Jang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Tumor Antigen ◽  
Polymer Nanoparticles ◽  
Antigen Delivery ◽  
Protein Polymer ◽  
Delivery Vehicles

We introduce virus-mimetic polymer nanoparticles as tumor antigen delivery vehicles to induce adjuvant-free cancer Ag specific-immune responses.

scholarly journals Combinations of Radiotherapy with Vaccination and Immune Checkpoint Inhibition Differently Affect Primary and Abscopal Tumor Growth and the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 714
Author(s):  
Michael Rückert ◽  
Lisa Deloch ◽  
Benjamin Frey ◽  
Eberhard Schlücker ◽  
Rainer Fietkau ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Immune Alterations ◽  
Tumor Cell Vaccines ◽  
Abscopal Effects

Radiotherapy (RT) is known to have immune-modulatory properties. We hypothesized that RT and inactivated whole tumor cell vaccines generated with high hydrostatic pressure (HHP) synergize to retard the tumor growth which can be additionally improved with anti-PD-1 treatment. In abscopal tumor models, we injected mice with B16-F10 melanoma or TS/A mammary tumors. To evaluate the efficiency of RT in combination with HHP vaccines, we locally irradiated only one tumor with 2 × 8 Gy or 3 × 8 Gy. HHP vaccines further retarded the growth of locally irradiated (2 × 8 Gy) tumors. However, HHP vaccination combined with RT failed to induce abscopal anti-tumor immune responses, namely those to non-irradiated tumors, and even partly abrogated those which were induced with RT plus anti-PD-1. In the latter group, the abscopal effects were accompanied by an elevated infiltration of CD8+ T cells, monocytes/macrophages, and dendritic cells. 3 × 8 Gy failed to induce abscopal effects in association with increased expression of immunosuppressive checkpoint molecules compared to 2 × 8 Gy. We conclude that HHP vaccines induce anti-tumor effects, but only if the tumor microenvironment was previously modulated by hypofractionated RT with not too many fractions, but failed to improve RT plus anti-PD-induced abscopal responses that are characterized by distinct immune alterations.

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