Immunological responses to adjuvant vaccination with combined CD1c<sup>+</sup> myeloid and plasmacytoid dendritic cells in stage III melanoma patients

Purpose of review Dendritic cells (DCs) are the gatekeepers of our immune system and indispensable in the antitumor immune response. In recent years, their classification has been revised considerably using single-cell sequencing approaches. In this review, we focus on their unique role in cancer and how specific DC subsets can be manipulated to induce an effective and durable antitumor response. Recent findings Historically, due to the ease of their isolation in sufficient cell numbers from peripheral blood, the utility of monocyte-derived DCs as therapeutic cancer vaccines was explored in the clinic. However, it became clear that naturally circulating myeloid DCs (myDC), exerting their physiological role, are a functionally more powerful cellular source of antigen presenting cells. With the advent of immunomagnetic bead technology to isolate naturally circulating DC subsets, the therapeutic value of these myDC subsets is currently being explored. Since DCs are also needed in the tumor microenvironment in order to “relicense” the activity of antitumor T cells, also intratumoral administration routes for DC vaccines are explored. In addition, to circumvent the use of expensive cellular vaccines, approaches to attract DCs to the tumor microenvironment are considered of interest in order to repair a defective cancer-immunity cycle. Summary In recent years, the type of DCs used for vaccination and their administration route evolved considerably. Intratumoral vaccination strategies require combination with additional stimuli to ensure proper functioning of DCs in the tumor microenvironment. Moreover, intratumoral administration limits the applicability to patients with accessible lesions.

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“…In 64% of the patients, functional IFN-γ-producing T cells were found in the skin test. Only low-grade adverse events were observed [40].…”

Section: Primary Naturally Circulating Dendritic Cells: More Potent V...mentioning

confidence: 98%

Current “state of the art” on dendritic cell-based cancer vaccines in melanoma

Schwarze

Geeraerts

Tuyaerts

et al. 2023

Current Opinion in Oncology

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“…A mixed response was described in one out of fifteen evaluable patients, but none obtained an overall tumor response. Other groups have reported that vaccination with natural classic and pDCs is safe and feasible [ 138 ]. Another innovative clinical trial selected Langerhans-type DC (CD83+ CD86 bright HLA-DR bright CD14 neg ) obtained ex vivo from CD34+ cells from the peripheral blood of resected stage IIB to IV melanoma patients.…”

Section: DC Vaccines In Solid Tumorsmentioning

confidence: 99%

Dendritic Cells in Cancer Immunology and Immunotherapy

Hato,

Vizcay,

Eguren

et al. 2024

Cancers

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Cancer immunotherapy modulates the immune system, overcomes immune escape and stimulates immune defenses against tumors. Dendritic cells (DCs) are professional promoters of immune responses against tumor antigens with the outstanding ability to coordinate the innate and adaptive immune systems. Evidence suggests that there is a decrease in both the number and function of DCs in cancer patients. Therefore, they represent a strong scaffold for therapeutic interventions. DC vaccination (DCV) is safe, and the antitumoral responses induced are well established in solid tumors. Although the addition of checkpoint inhibitors (CPIs) to chemotherapy has provided new options in the treatment of cancer, they have shown no clinical benefit in immune desert tumors or in those tumors with dysfunctional or exhausted T-cells. In this way, DC-based therapy has demonstrated the ability to modify the tumor microenvironment for immune enriched tumors and to potentiate systemic host immune responses as an active approach to treating cancer patients. Application of DCV in cancer seeks to obtain long-term antitumor responses through an improved T-cell priming by enhancing previous or generating de novo immune responses. To date, DCV has induced immune responses in the peripheral blood of patients without a significant clinical impact on outcome. Thus, improvements in vaccines formulations, selection of patients based on biomarkers and combinations with other antitumoral therapies are needed to enhance patient survival. In this work, we review the role of DCV in different solid tumors with their strengths and weaknesses, and we finally mention new trends to improve the efficacy of this immune strategy.

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“…Although cDCs may be superior to MoDCs in their ability to stimulate T cells (7,103), there are currently no established protocols for isolating or differentiating these cells in vitro. Nonetheless, in some diseases, most notably melanoma, the use of cDCs and pDCs as DC vaccines has shown some encouraging early results that may be extended to GBM research in the future (104)(105)(106)(107).…”

Section: Overview Of DCV Clinical Trials 41 the Source Of Dcsmentioning

confidence: 99%

Dendritic cell vaccine of gliomas: challenges from bench to bed

Zheng,

Ma,

Feng

et al. 2023

Front. Immunol.

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Gliomas account for the majority of brain malignant tumors. As the most malignant subtype of glioma, glioblastoma (GBM) is barely effectively treated by traditional therapies (surgery combined with radiochemotherapy), resulting in poor prognosis. Meanwhile, due to its “cold tumor” phenotype, GBM fails to respond to multiple immunotherapies. As its capacity to prime T cell response, dendritic cells (DCs) are essential to anti-tumor immunity. In recent years, as a therapeutic method, dendritic cell vaccine (DCV) has been immensely developed. However, there have long been obstacles that limit the use of DCV yet to be tackled. As is shown in the following review, the role of DCs in anti-tumor immunity and the inhibitory effects of tumor microenvironment (TME) on DCs are described, the previous clinical trials of DCV in the treatment of GBM are summarized, and the challenges and possible development directions of DCV are analyzed.

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Immunological responses to adjuvant vaccination with combined CD1c⁺ myeloid and plasmacytoid dendritic cells in stage III melanoma patients

Cited by 17 publications

References 66 publications

Current “state of the art” on dendritic cell-based cancer vaccines in melanoma

Current “state of the art” on dendritic cell-based cancer vaccines in melanoma

Dendritic Cells in Cancer Immunology and Immunotherapy

Dendritic cell vaccine of gliomas: challenges from bench to bed

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Immunological responses to adjuvant vaccination with combined CD1c+ myeloid and plasmacytoid dendritic cells in stage III melanoma patients

Cited by 17 publications

References 66 publications

Current “state of the art” on dendritic cell-based cancer vaccines in melanoma

Current “state of the art” on dendritic cell-based cancer vaccines in melanoma

Dendritic Cells in Cancer Immunology and Immunotherapy

Dendritic cell vaccine of gliomas: challenges from bench to bed

Contact Info

Product

Resources

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Immunological responses to adjuvant vaccination with combined CD1c⁺ myeloid and plasmacytoid dendritic cells in stage III melanoma patients