Tumor cell-derived autophagosomes (DRibbles)-activated B cells induce specific naïve CD8+ T cell response and exhibit antitumor effect

Zhang, Tianyu; Ren, Hongyan; Pan, Ning; Dong, Huixia; Zhao, Simin; Zhang, Wen; Wang, Xuru; Wang, Lixin

doi:10.1007/s00262-020-02695-5

Cited by 6 publications

(7 citation statements)

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“…We have reported that DRibbles-contained antigens could be present to activate effect and naïve T cells by DRibbles-activated B cells in mice ( 15 , 16 ). To investigate whether DRibbles-loaded human B cells could also effectively activate antigen-specific memory T cells, purified human B cells from PBMCs of CMV positive donors were used as APCs and exposed to CMVpp65 + DRibbles, control GFP + DRibbles or pp65 protein.…”

Section: Resultsmentioning

confidence: 99%

“…HMGB1(the high-mobility group box 1 protein), functions as a damage-associated molecular pattern (DAMP), has been found enriched in and present on the surface of DRibbles ( 16 ). And our group has confirmed that HMGB1 was essential for mouse B cell activation ( 16 ). Based on these findings, we hypothesized that HMGB1 on DRibbles might play an important role in human B cells activation also.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous studies showed that many DAMP (damage-associated molecular pattern) molecules, such as HSP90 (heat shock protein), HSP94 and HMGB1, were present in DRibbles ( 6 – 8 , 16 ). In this study, we further confirmed that HMGB1on DRibbles was responsible for human B cells activation and subsequent enhanced T-cell responses induced by DRibbles-loaded B Cells.…”

Section: Discussionmentioning

confidence: 99%

“…What's more, compared with DCs, it is easier to isolate and amplify B cells from non-stem cell sources in vitro (11)(12)(13). Therefore, our previous studies with mouse tumor models have proved that DRibbles could activate mouse naïve B-cell and DRibblescontained antigens could be present by the activated B cells to stimulate effector and naïve T cells (14)(15)(16). However, the effect of DRibbles on human B cells remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Tumor-Derived Autophagosomes (DRibbles) Activate Human B Cells to Induce Efficient Antigen-Specific Human Memory T-Cell Responses

et al. 2021

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We have reported that tumor-derived autophagosomes (DRibbles) were efficient carriers of tumor antigens and DRibbles antigens could be present by DRibbles-activated B cells to stimulate effect and naïve T cells in mice. However, the effect of DRibbles on human B cells remains unclear. Herein, we found that DRibbles can also efficiently induce proliferation and activation of human B cells and lead to the production of chemokines, cytokines and hematopoietic growth factors. We further demonstrated human B cells can effectively phagocytose DRibbles directly and cross-present DRibbles antigens to stimulate antigen-specific memory T cells. Furthermore, we found that membrane-bound high-mobility group B1 (HMGB1) on DRibbles was crucial for inducing human B cells activation. Therefore, these findings provide further evidence to promote the clinical application of B-DRibbles vaccines.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor-Derived Autophagosomes (DRibbles) Activate Human B Cells to Induce Efficient Antigen-Specific Human Memory T-Cell Responses

et al. 2021

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“…Autophagy is also important for the T cell biology: it supports the activation, proliferation, function, and memory maintenance of these cells [ 218 , 219 ]. Similarly, autophagy is fundamental for B cells since a lack of autophagy attenuates the secondary immune response, antigen presenting and processing, and the differentiation of plasma cells [ 220 ]. Finally, autophagy controls the functions of dendritic cells, the activity of myeloid derived suppressor cells (MDSCs), and regulates the formation, maintenance, recruitment, and polarization of macrophages [ 208 ].…”

Section: Autophagy and Tumor Immune Responsementioning

confidence: 99%

Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers

Patergnani

Missiroli

Morciano

et al. 2021

Cancers

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The malignant transformation of a cell produces the accumulation of several cellular adaptions. These changes determine variations in biological processes that are necessary for a cancerous cell to survive during stressful conditions. Autophagy is the main nutrient recycling and metabolic adaptor mechanism in eukaryotic cells, represents a continuous source of energy and biomolecules, and is fundamental to preserve the correct cellular homeostasis during unfavorable conditions. In recent decades, several findings demonstrate a close relationship between autophagy, malignant transformation, and cancer progression. The evidence suggests that autophagy in the cancer context has a bipolar role (it may act as a tumor suppressor and as a mechanism of cell survival for established tumors) and demonstrates that the targeting of autophagy may represent novel therapeutic opportunities. Accordingly, the modulation of autophagy has important clinical benefits in patients affected by diverse cancer types. Currently, about 30 clinical trials are actively investigating the efficacy of autophagy modulators to enhance the efficacy of cytotoxic chemotherapy treatments. A deeper understanding of the molecular pathways regulating autophagy in the cancer context will provide new ways to target autophagy for improving the therapeutic benefits. Herein, we describe how autophagy participates during malignant transformation and cancer progression, and we report the ultimate efforts to translate this knowledge into specific therapeutic approaches to treat and cure human cancers.

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Recent Advances in Delivery Systems for Genetic and Other Novel Vaccines

et al. 2022

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including yellow fever, polio, diphtheria, rubella, smallpox, mumps, and measles in humans; and equine infectious anemia, classic swine fever, and cattle plague in animals. The successful prevention of these diseases has saved millions of lives, as well as time and efforts in health care. However, conventional vaccines are usually not effective as therapeutic measures, and often fail to provide sufficient protections against some diseases. Therefore, many major diseases, such as the malaria, tuberculosis, dengue, human immunodeficiency virus (HIV) infections, and cancer, still lack effective vaccines, and developing vaccines for them remains challenging. [5][6][7] Though many autoimmune diseases are also difficult to vaccinate, we excluded this type of diseases in the review due to their highly variable and unique mechanisms.There are various factors that may influence the outcomes of vaccines. An important discovery of modern immunology is that robust cellular immune responses with strong CD8 + T cell activities may significantly improve vaccination outcome against some of these hard-to-vaccinate diseases. This is particularly the case when the pathogens can lurk in infected cells for a long period of time (e.g., HIV) or the cells themselves became malfunctional (e.g., cancer). However, conventional vaccines often suffer from imprecise control of vaccine activity in vivo (e.g., targeted accumulation and selective cell uptake) which leads to insufficient/inappropriate immune responses or short immune memory; hence, they may become less effective in these situations. [7][8][9] Besides, rapid vaccine development, targeted epitope optimization, and other novel strategies are regarded to be important for successful prevention of infections from viral pathogens with high mutation rates (e.g., the highly variable influenza virus) which often quickly become resistant to existing vaccines. [10,11] With the advances in biological and pharmaceutical technologies, a series of new vaccines have been developed, including the famous subunit vaccines (including bioengineered protein, protein fragments, and peptides) and genetic vaccines (normally DNA-and RNA-based vaccines). These alternative vaccines provide new possibilities for preventing hard-to-vaccinate diseases by using carefully selected components of the pathogens or diseased cells as vaccine immunogens based on in-depth understanding of the immune response activation processes. More specifically, characteristic proteins/peptides Vaccination is one of the most successful and cost-effective prophylactic measures against diseases, especially infectious diseases including smallpox and polio. However, the development of effective prophylactic or therapeutic vaccines for other diseases such as cancer remains challenging. This is often due to the imprecise control of vaccine activity in vivo which leads to insufficient/inappropriate immune responses or short immune memory. The development of new vaccine types in recent decades has created the potential for improving the prot...

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Tumor cell-derived autophagosomes (DRibbles)-activated B cells induce specific naïve CD8+ T cell response and exhibit antitumor effect

Cited by 6 publications

References 36 publications

Tumor-Derived Autophagosomes (DRibbles) Activate Human B Cells to Induce Efficient Antigen-Specific Human Memory T-Cell Responses

Tumor-Derived Autophagosomes (DRibbles) Activate Human B Cells to Induce Efficient Antigen-Specific Human Memory T-Cell Responses

Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers

Recent Advances in Delivery Systems for Genetic and Other Novel Vaccines

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