Tumor-Derived Extracellular Vesicles Impair CD171-Specific CD4+ CAR T Cell Efficacy

Ali, Solin; Toews, Karin; Schwiebert, Silke; Klaus, Anika; Winkler, Annika; Grunewald, Laura; Oevermann, Lena; Deubzer, Hedwig E.; Tüns, Alicia I.; Jensen, Michael C.; Henssen, Anton; Eggert, Angelika; Schulte, Johannes H.; Schwich, Esther; Rebmann, Vera; Schramm, Alexander; Künkele, Annette

doi:10.3389/fimmu.2020.00531

Cited by 28 publications

(21 citation statements)

References 43 publications

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“…However, EVs are used for immune modulation by pathogens as well. Several methods of how pathogens try to compromise the immune system by bacterial EVs [ 38 ] or by hijacking exosomes by viruses [ 39 ] or by impairing T-cell efficacy [ 40 ] have been described.…”

Section: Introductionmentioning

confidence: 99%

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

Kolonics

Szeifert

Tímár

et al. 2020

Cells

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Similar to other cell types, neutrophilic granulocytes also release extracellular vesicles (EVs), mainly medium-sized microvesicles/microparticles. According to published data, authors have reached a consensus on the physical parameters (size, density) and chemical composition (surface proteins, proteomics) of neutrophil-derived EVs. In contrast, there is large diversity and even controversy in the reported functional properties. Part of the discrepancy may be ascribed to differences in the viability of the starting cells, in eliciting factors, in separation techniques and in storage conditions. However, the most recent data from our laboratory prove that the same population of neutrophils is able to generate EVs with different functional properties, transmitting pro-inflammatory or anti-inflammatory effects on neighboring cells. Previously we have shown that Mac-1 integrin is a key factor that switches anti-inflammatory EV generation into pro-inflammatory and antibacterial EV production. This paper reviews current knowledge on the functional alterations initiated by neutrophil-derived EVs, listing their effects according to the triggering agents and target cells. We summarize the presence of neutrophil-derived EVs in pathological processes and their perspectives in diagnostics and therapy. Finally, the functional heterogeneity of differently triggered EVs indicates that neutrophils are capable of producing a broad spectrum of EVs, depending on the environmental conditions prevailing at the time of EV genesis.

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Section: Introductionmentioning

confidence: 99%

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

Kolonics

Szeifert

Tímár

et al. 2020

Cells

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“…According to Laurent et al (2016), TDEs decreased the expression of CD69 on the surface of activated CD4 + T cells, and increased adenosine production of Tregs in a ligand-receptor, but not internalized pattern 16 . For CAR T cell-based therapy in the treatment of neuroblastoma, TDEs counteracted the effects of CD4 + T cells, but not CD8 + T cells 17 .…”

Section: Cd4 + T-cellsmentioning

confidence: 96%

The role of tumor-derived exosomes in tumor immune escape: A concise review

et al. 2020

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Exosomes are small vesicles secreted by viable cells into the microenvironment. These vesicles bring various compositions, including lipids, RNAs and proteins, which carry information from producer cells to target cells. Cancer cells also produce exosomes, termed as tumor-derived exosomes (TDEs), which play important roles in immune modulation, angiogenesis and metastasis of tumors. This review summarizes the roles of TDEs in tumor immune escape mechanisms. TDEs affect all kinds of tumor-associated immune cells, including natural killer (NK) cells, dendritic cells (DCs), T and B lymphocytes, and myeloid-derived suppressor cells (MDSCs). Generally, TDEs suppress the immune system to promote tumor immune escape, thereby significantly contributing to tumorigenesis and metastasis.

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“…The ability of NB-derived EV to dampen tumor-specific T cell responses was also addressed by Ali and coworkers [63]. They characterized NB-derived EV, demonstrating the expression of CD81 tetraspanin, syntenin and TSG101 cytosolic proteins on the EV preparation.…”

Section: Immunosuppressive Functions Of Nb-derived Evmentioning

confidence: 97%

The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

Marimpietri

Airoldi

Faini

et al. 2021

IJMS

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The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. The ability of extracellular vesicles to cross-talk with different cells in the tumor microenvironment and to modulate an anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance will be pinpointed in detail. The results obtained on the role of extracellular vesicles may represent a panel of suggestions potentially useful in practice, due to their involvement in the response to chemotherapy, and, moreover, their ability to predict resistance to standard therapies—all issues of clinical relevance.

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Tumor-Derived Extracellular Vesicles Impair CD171-Specific CD4+ CAR T Cell Efficacy

Cited by 28 publications

References 43 publications

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

The role of tumor-derived exosomes in tumor immune escape: A concise review

The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

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