Vaccination with dendritic cells charged with apoptotic/necrotic B16 melanoma induces the formation of subcutaneous lymphoid tissue

Keon, Soledad Mac; Gazzaniga, Silvina; Mallerman, Julieta; Bravo, Alicia; Mordoh, José; Wainstok, Rosa

doi:10.1016/j.vaccine.2010.09.095

Cited by 16 publications

(16 citation statements)

References 27 publications

(32 reference statements)

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“…Keratinocytes may also be involved in local APC inflammatory activation through the secretion of the active form of IL-1β, as well as in suppressive imprinting through transforming growth factor (TGF)-β1 production. Therefore, the immunological balance within the newly formed structure at the site of DC-based vaccine injection, observed both in mice (45) and humans (46), must be delicately studied. One study reports that repeated vaccination with melanoma peptides in incomplete Freund’s adjuvant (IFA) induced organized and persistent lymphoid aggregates in the patients’ dermis.…”

Section: Vaccine Administration: Immune Role For the Injection Sitementioning

confidence: 99%

Dendritic Cell-Based Vaccine Efficacy: Aiming for Hot Spots

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2015

Front. Immunol.

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Many approaches for cancer immunotherapy have targeted dendritic cells (DCs), directly or indirectly, for the induction of antitumor immune responses. DC-based vaccines have been developed using a wide variety of ex vivo DC culture conditions, antigen (Ag) source and loading strategies, maturation agents, and routes of vaccination. Adjuvants are used to activate innate immune cells at the vaccine injection site, to promote Ag transport to the draining lymph nodes (LNs) and to model adaptive immune responses. Despite years of effort, the effective induction of strong and durable antitumor T-cell responses in vaccinated patients remains a challenge. The study of vaccine interactions with other immune cells in the LNs and, more recently, in the injection site has opened new doors for understanding antitumor effector T-cell licensing and function. In this review, we will briefly discuss the relevant sites and up-to-date facts regarding possible targets for antitumor vaccine refinement. We will focus on the processes taking place at the injection site, adjuvant combinations and their role in DC-based vaccines, LN homing, and modeling vaccine-induced immune responses capable of controlling tumor growth and generating immune memory.

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Section: Vaccine Administration: Immune Role For the Injection Sitementioning

confidence: 99%

Dendritic Cell-Based Vaccine Efficacy: Aiming for Hot Spots

Pizzurro

Barrio

2015

Front. Immunol.

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“…Thus, there is no demonstration that clinical grade human macrophages can efficiently cross-present naturally-occurring tumor antigens and, if so, how it compares with the well-documented cross-presentation achieved by human DC prepared for therapeutic use. Of note, when mice were vaccinated with DC loaded with apoptotic/necrotic B16 cells (DC-Apo/Nec), a tertiary lymphoid structure was generated at the vaccination site that contained a wide variety of cell populations, including macrophages, polymorphonuclear cells, as well as CD4 + and CD8 + T lymphocytes found together with DC [30]. This suggests that macrophages could also contribute to the antitumor response against gamma-irradiated tumor cells locally, or after migration to the lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Human Macrophages and Dendritic Cells Can Equally Present MART-1 Antigen to CD8+ T Cells after Phagocytosis of Gamma-Irradiated Melanoma Cells

et al. 2012

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Dendritic cells (DC) can achieve cross-presentation of naturally-occurring tumor-associated antigens after phagocytosis and processing of dying tumor cells. They have been used in different clinical settings to vaccinate cancer patients. We have previously used gamma-irradiated MART-1 expressing melanoma cells as a source of antigens to vaccinate melanoma patients by injecting irradiated cells with BCG and GM-CSF or to load immature DC and use them as a vaccine. Other clinical trials have used IFN-gamma activated macrophage killer cells (MAK) to treat cancer patients. However, the clinical use of MAK has been based on their direct tumoricidal activity rather than on their ability to act as antigen-presenting cells to stimulate an adaptive antitumor response. Thus, in the present work, we compared the fate of MART-1 after phagocytosis of gamma-irradiated cells by clinical grade DC or MAK as well as the ability of these cells to cross present MART-1 to CD8+ T cells. Using a high affinity antibody against MART-1, 2A9, which specifically stains melanoma tumors, melanoma cell lines and normal melanocytes, the expression level of MART-1 in melanoma cell lines could be related to their ability to stimulate IFN-gamma production by a MART-1 specific HLA-A*0201-restricted CD8+ T cell clone. Confocal microscopy with Alexa Fluor®647-labelled 2A9 also showed that MART-1 could be detected in tumor cells attached and/or fused to phagocytes and even inside these cells as early as 1 h and up to 24 h or 48 h after initiation of co-cultures between gamma-irradiated melanoma cells and MAK or DC, respectively. Interestingly, MART-1 was cross-presented to MART-1 specific T cells by both MAK and DC co-cultured with melanoma gamma-irradiated cells for different time-points. Thus, naturally occurring MART-1 melanoma antigen can be taken-up from dying melanoma cells into DC or MAK and both cell types can induce specific CD8+ T cell cross-presentation thereafter.

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“…Signals that instigate the diffuse-to-organized structural transition of TLO may be provided by cognate T cell recognition of relevant target cell populations within nascent TLO (15, 72). It is important to note, however, that immature TLO have been oft-associated with locoregional immune sequelae including manifestations of autoimmunity and anti-tumor efficacy (5, 32, 71).…”

Section: Slo/tlo Development: Natural and Inducedmentioning

confidence: 99%

“…It also appears that the administration of appropriately activated/engineered DC is sufficient to nucleate and/or maintain the development of TLO in vivo (36, 72). For instance, mice vaccinated sub-cutaneously with syngenic DC loaded with apoptotic/necrotic B16 melanoma cell debris develop operational TLO [pseudocapsule; PNAd + vascular endothelial cells (VEC), T cell/DC infiltrates] at sites of injection, leading to the activation of protective anti-tumor immunity (72).…”

Section: Use Of Dc-based Therapy To Promote Extranodal Priming Of Antmentioning

confidence: 99%

“…For instance, mice vaccinated sub-cutaneously with syngenic DC loaded with apoptotic/necrotic B16 melanoma cell debris develop operational TLO [pseudocapsule; PNAd + vascular endothelial cells (VEC), T cell/DC infiltrates] at sites of injection, leading to the activation of protective anti-tumor immunity (72). DC genetically engineered to secrete high-levels of CCL21 (DC.CCL21) and injected directly into B16 murine melanomas promote strong extranodal T cell cross-priming/recruitment into the TME, even in LTα −/− mice that lack SLO (8, 68).…”

Section: Use Of Dc-based Therapy To Promote Extranodal Priming Of Antmentioning

confidence: 99%

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Therapeutic Use of Dendritic Cells to Promote the Extranodal Priming of Anti-Tumor Immunity

et al. 2013

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Ectopic lymphoid tissue, also known as tertiary lymphoid organs (TLO) develop adaptively within sites of chronic tissue inflammation, thereby allowing the host to efficiently crossprime specific immune effector cells within sites of disease. Recent evidence suggests that the presence of TLO in the tumor microenvironment (TME) predicts better overall survival. We will discuss the relevance of extranodal T cell priming within the TME as a means to effectively promote anti-tumor immunity and the strategic use of dendritic cell (DC)-based therapies to reinforce this clinically preferred process in the cancer-bearing host.

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Vaccination with dendritic cells charged with apoptotic/necrotic B16 melanoma induces the formation of subcutaneous lymphoid tissue

Cited by 16 publications

References 27 publications

Dendritic Cell-Based Vaccine Efficacy: Aiming for Hot Spots

Dendritic Cell-Based Vaccine Efficacy: Aiming for Hot Spots

Human Macrophages and Dendritic Cells Can Equally Present MART-1 Antigen to CD8+ T Cells after Phagocytosis of Gamma-Irradiated Melanoma Cells

Therapeutic Use of Dendritic Cells to Promote the Extranodal Priming of Anti-Tumor Immunity

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