The avidity of tumor‐specific T cells amplified by a plasmacytoid dendritic cell‐based assay can predict the clinical evolution of melanoma patients

Charles, J.; Chaperot, Laurence; Revol, Bruno; Baudin, Marine; Mouret, Stéphane; Hamon, Agnès; Leccia, Marie‐Thérèse; Plumas, Joël; Aspord, Caroline

doi:10.1111/pcmr.12618

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…The most exciting part of this clinical trial is that pDCs were obtained from a human pDC cell line instead of autologous pDCs from patients. This proprietary allogeneic plasmacytoid dendritic cell line is derived from malignant leukemic cells of a pDC leukemia patient, and have been shown to induce antigen-specific T cell responses in pre-clinical studies [ 100 , 101 , 102 ]. Two clinical batches of pDC cell line were generated from the primary cell bank, and then were amplified in CellSTACK Chambers.…”

Section: Current Pdc-based Cancer Vaccine Clinical Trialsmentioning

confidence: 99%

Plasmacytoid Dendritic Cells and Cancer Immunotherapy

Zhou

et al. 2022

Cells

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Despite largely disappointing clinical trials of dendritic cell (DC)-based vaccines, recent studies have shown that DC-mediated cross-priming plays a critical role in generating anti-tumor CD8 T cell immunity and regulating anti-tumor efficacy of immunotherapies. These new findings thus support further development and refinement of DC-based vaccines as mono-immunotherapy or combinational immunotherapies. One exciting development is recent clinical studies with naturally circulating DCs including plasmacytoid DCs (pDCs). pDC vaccines were particularly intriguing, as pDCs are generally presumed to play a negative role in regulating T cell responses in tumors. Similarly, DC-derived exosomes (DCexos) have been heralded as cell-free therapeutic cancer vaccines that are potentially superior to DC vaccines in overcoming tumor-mediated immunosuppression, although DCexo clinical trials have not led to expected clinical outcomes. Using a pDC-targeted vaccine model, we have recently reported that pDCs required type 1 conventional DCs (cDC1s) for optimal cross-priming by transferring antigens through pDC-derived exosomes (pDCexos), which also cross-prime CD8 T cells in a bystander cDC-dependent manner. Thus, pDCexos could combine the advantages of both cDC1s and pDCs as cancer vaccines to achieve better anti-tumor efficacy. In this review, we will focus on the pDC-based cancer vaccines and discuss potential clinical application of pDCexos in cancer immunotherapy.

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Section: Current Pdc-based Cancer Vaccine Clinical Trialsmentioning

confidence: 99%

Plasmacytoid Dendritic Cells and Cancer Immunotherapy

Zhou

et al. 2022

Cells

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Dendritic Cell-Based Vaccines Against Cancer: Challenges, Advances and Future Opportunities

Zhou

et al. 2022

Immunological Investigations

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DC-Based Vaccines for Cancer Immunotherapy

Zhou

et al. 2020

Vaccines

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As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process that DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHCI (Major Histocompatibility Complex class I), plays a critical role in mediating CD8 T cell immunity as well as tolerance. Current DC vaccines have remained largely unsuccessful despite their ability to potentiate both effector and memory CD8 T cell responses. There are two major hurdles for the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitation of the commonly used monocyte-derived dendritic cells (MoDCs). Due to their resistance to tumor-mediated suppression as inert vesicles, DC-derived exosomes (DCexos) have garnered much interest as cell-free therapeutic agents. However, current DCexo clinical trials have shown limited clinical benefits and failed to generate antigen-specific T cell responses. Another exciting development is the use of naturally circulating DCs instead of in vitro cultured DCs, as clinical trials with both human blood cDC2s (type 2 conventional DCs) and plasmacytoid DCs (pDCs) have shown promising results. pDC vaccines were particularly encouraging, especially in light of promising data from a recent clinical trial using a human pDC cell line, despite pDCs being considered tolerogenic and playing a suppressive role in tumors. However, how pDCs generate anti-tumor CD8 T cell immunity remains poorly understood, thus hindering their clinical advance. Using a pDC-targeted vaccine model, we have recently reported that while pDC-targeted vaccines led to strong cross-priming and durable CD8 T cell immunity, cross-presenting pDCs required cDCs to achieve cross-priming in vivo by transferring antigens to cDCs. Antigen transfer from pDCs to bystander cDCs was mediated by pDC-derived exosomes (pDCexos), which similarly required cDCs for cross-priming of antigen-specific CD8 T cells. pDCexos thus represent a new addition in our arsenal of DC-based cancer vaccines that would potentially combine the advantage of pDCs and DCexos.

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The avidity of tumor‐specific T cells amplified by a plasmacytoid dendritic cell‐based assay can predict the clinical evolution of melanoma patients

Cited by 3 publications

References 49 publications

Plasmacytoid Dendritic Cells and Cancer Immunotherapy

Plasmacytoid Dendritic Cells and Cancer Immunotherapy

Dendritic Cell-Based Vaccines Against Cancer: Challenges, Advances and Future Opportunities

DC-Based Vaccines for Cancer Immunotherapy

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