OX40+ plasmacytoid dendritic cells in the tumor microenvironment promote antitumor immunity

Poropatich, Kate; Dominguez, Donye; Chan, Wen-Ching; Andrade, Jorge; Zha, Yuanyuan; Wray, Brian; Miska, Jason; Qin, Lei; Cole, Lisa E.; Coates, Sydney; Patel, Urjeet A.; Samant, Sandeep; Zhang, Bin

doi:10.1172/jci131992

Cited by 66 publications

(66 citation statements)

References 61 publications

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“…PDCs can exert also indirect antitumor effects through the CCR5-mediated recruitment of NK cells and the OX40L-mediated induction of IFN-γ [69]. In head and neck squamous carcinoma, a morphologically, functionally, and transcriptionally unique pDC subset expressing high levels of OX40 was described for being able to synergize with cDCs in generating potent tumor antigen specific CD8 + T cell responses [70].…”

Section: Anti-tumor Activity Of DC Subsetsmentioning

confidence: 99%

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Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

Prete

Sozio

Barbazza

et al. 2020

IJMS

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Dendritic cells (DCs) constitute a complex network of cell subsets with common functions but also with many divergent aspects. All dendritic cell subsets share the ability to prime T cell response and to undergo a complex trafficking program related to their stage of maturation and function. For these reasons, dendritic cells are implicated in a large variety of both protective and detrimental immune responses, including a crucial role in promoting anti-tumor responses. Although cDC1s are the most potent subset in tumor antigen cross-presentation, they are not sufficient to induce full-strength anti-tumor cytotoxic T cell response and need close interaction and cooperativity with the other dendritic cell subsets, namely cDC2s and pDCs. This review will take into consideration different aspects of DC biology, including the functional role of dendritic cell subsets in both fostering and suppressing tumor growth, the mechanisms underlying their recruitment into the tumor microenvironment, as well as the prognostic value and the potentiality of dendritic cell therapeutic targeting. Understanding the specificity of dendritic cell subsets will allow to gain insights on role of these cells in pathological conditions and to design new selective promising therapeutic approaches.

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Section: Anti-tumor Activity Of DC Subsetsmentioning

confidence: 99%

“…was described for being able to synergize with cDCs in generating potent tumor antigen specific CD8 + T cell responses [70]. Because of the high degree of overlap with other myeloid cells, the relevance of moDCs in human tumors is unclear.…”

Section: Anti-tumor Activity Of DC Subsetsmentioning

confidence: 99%

Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

Prete

Sozio

Barbazza

et al. 2020

IJMS

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“…More recently, OX40-positive plasmacytoid DCs (major producers of IFN-I) were discovered to promote anti-tumour immunity in the TME [238]. pDCs are major producers of antiviral type I interferon (IFN-I).…”

Section: Ox40-positive Regulatory T Cells and Plasmacytoid Dcsmentioning

confidence: 99%

“…pDCs are major producers of antiviral type I interferon (IFN-I). However, recently it was reported that a subset of naturally occurring OX40+pDCs increase local IL-12 and IFN-α production and enhances anti-tumour conventional DCs (lymphoid-tissue resident) and CD8+ T cells interactions in vivo in the TME of head and neck carcinomas [238]. Interestingly, Lu et al reported a key anti-tumour role for IFN-I in enhancing cytotoxic T cell effector function in suppressing tumour development [239], which may coincide with the effect of the recently discovered OX40+pDCs.…”

Section: Ox40-positive Regulatory T Cells and Plasmacytoid Dcsmentioning

confidence: 99%

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets

Alard

Butnariu

Grillo

et al. 2020

Cancers

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Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient’s own immune system to selectively kill cancer cells. The immune system is the body’s main cancer surveillance system, but cancers may evade destruction thanks to various immune-suppressing mechanisms. We therefore need to deploy various immunotherapy-based strategies to help bolster the anti-tumour immune responses. These include engineering T cells to express chimeric antigen receptors (CARs) to specifically recognise tumour neoantigens, inactivating immune checkpoints, oncolytic viruses and dendritic cell (DC) vaccines, which have all shown clinical benefit in certain cancers. However, treatment efficacy remains poor due to drug-induced adverse events and immunosuppressive tendencies of the tumour microenvironment. Recent preclinical studies have unveiled novel therapies such as anti-cathepsin antibodies, galectin-1 blockade and anti-OX40 agonistic antibodies, which may be utilised as adjuvant therapies to modulate the tumour microenvironment and permit more ferocious anti-tumour immune response.

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“…pDCs are also capable of exerting indirect antitumor immunity by the OX40L-mediated production of IFNγ and the CCR5-mediated recruitment of NKs [ 65 ]. A unique subset of pDCs were identified in head and neck squamous carcinoma that overexpress OX40 and was reported to demonstrate synergizing effects with cDCs in inducing effective TAA-specific CD8 + T cell responses [ 66 ].…”

Section: Introductionmentioning

confidence: 99%

Dexosomes as a cell-free vaccine for cancer immunotherapy

Nikfarjam

Rezaie

Kashanchi

et al. 2020

J Exp Clin Cancer Res

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Dendritic cells (DCs) secrete vast quantities of exosomes termed as dexosomes. Dexosomes are symmetric nanoscale heat-stable vesicles that consist of a lipid bilayer displaying a characteristic series of lipid and protein molecules. They include tetraspanins and all established proteins for presenting antigenic material such as the major histocompatibility complex class I/II (MHC I/II) and CD1a, b, c, d proteins and CD86 costimulatory molecule. Dexosomes contribute to antigen-specific cellular immune responses by incorporating the MHC proteins with antigen molecules and transferring the antigen-MHC complexes and other associated molecules to naïve DCs. A variety of ex vivo and in vivo studies demonstrated that antigen-loaded dexosomes were able to initiate potent antitumor immunity. Human dexosomes can be easily prepared using monocyte-derived DCs isolated by leukapheresis of peripheral blood and treated ex vivo by cytokines and other factors. The feasibility of implementing dexosomes as therapeutic antitumor vaccines has been verified in two phase I and one phase II clinical trials in malignant melanoma and non small cell lung carcinoma patients. These studies proved the safety of dexosome administration and showed that dexosome vaccines have the capacity to trigger both the adaptive (T lymphocytes) and the innate (natural killer cells) immune cell recalls. In the current review, we will focus on the perspective of utilizing dexosome vaccines in the context of cancer immunotherapy.

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OX40+ plasmacytoid dendritic cells in the tumor microenvironment promote antitumor immunity

Cited by 66 publications

References 61 publications

Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets

Dexosomes as a cell-free vaccine for cancer immunotherapy

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