Dendritic cell-based immunogens for B-cell chronic lymphocytic leukemia

Allgeier, Thomas; Garhammer, Silke; Nößner, Elfriede; Wahl, Ulrich; Kronenberger, Konrad; Dreyling, Martin; Hallek, Michael; Mocikat, Ralph

doi:10.1016/j.canlet.2006.01.019

Cited by 8 publications

(2 citation statements)

References 33 publications

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“…DCs are crucial in inducing tumor-specific immune responses, particularly through presentation of major histocompatibility complex-class I antigens and cytotoxic T cell production (12). DC-based tumor immunization represents a novel experimental immunotherapeutic approach in (13).…”

Section: Introductionmentioning

confidence: 99%

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand�1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

et al. 2019

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Programmed death receptor ligand 1 (PD-L1), which belongs to the B7 family, is overexpressed in a variety of human cancer types and serves a crucial role in immune escape by malignant cells. Programmed death receptor 1 (PD-1) is a specific PD-L1 receptor. PD-1/PD-L1 signaling inhibits the antitumor effects of dendritic cell (DC) immunization for tumor treatment. The aim of the present study was to determine whether inhibiting PD-L1 may increase the immunologic anti-tumor effect of dendritic cells against pancreatic cancer. In the present study, PD-L1 levels in non-cancerous and malignant tissue samples were compared, and the impact of PD-L1 downregulation on human pancreatic cancer PaTu8988 cells was determined by lentivirus-based RNA interference and DC immunotherapy. PD-L1 expression in pancreatic specimens was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. PaTu8988 cells expressing reduced levels of PD-L1 were generated by lentivirus-based knockdown to assess the mechanism by which the inhibition of PD-L1 signaling in DC immunization affects therapeutic outcomes in pancreatic cancer-bearing SCID-hu mice. PD-L1 levels were markedly elevated in pancreatic adenocarcinoma samples compared with in non-cancerous tissue. PD-L1 silencing in pancreatic adenocarcinoma cells resulted in improved treatment outcomes of DC immunization in vitro and in vivo compared with traditional DC immunization. PD-L1 silencing enhances the antitumor response of cytotoxic T cells by increasing interferon γ production in vitro . In vivo , this method prevented tumor growth and lung metastasis, and prolonged survival in the SCID-hu model. In conclusion, the results of the present study suggested that suppressing PD-L1 in malignant cells during DC immunization may be a useful tool for immunotherapy in pancreatic adenocarcinoma.

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Section: Introductionmentioning

confidence: 99%

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand�1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

et al. 2019

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“…Dendritic cells (DCs) have a unique ability to efficiently present antigens to naïve T cells and are key players in the initiation and regulation of innate and adoptive immune responses [4]. There are several preclinical studies regarding ex vivo ‐generated DCs as potential vaccines against CLL [5–10] because this could be a strategy to circumvent the immune defects [11] and the reported dysfunction of DCs in patients with CLL [12]. However, to enable T helper 1 (Th1) and cytotoxic T cell (CTL) induction and antitumour responses in vivo , a DC has to present relevant tumour antigens in combination with costimulatory molecules [13].…”

Section: Introductionmentioning

confidence: 99%

Tumour‐loaded α‐type 1‐polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia Produce a Superior NK‐, NKT‐ and CD8⁺ T Cell‐attracting Chemokine Profile

et al. 2011

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Tumour‐loaded dendritic cells (DCs) from patients with chronic lymphocytic leukaemia (CLL) matured using an α‐type 1‐polarized DC cocktail (IL‐1β/TNF‐α/IFN‐α/IFN‐γ/poly‐I:C;αDC1) were recently shown to induce more functional CD8+ T cells against autologous tumour cells in vitro than DCs matured with the ‘standard’ cocktail (IL‐1β/TNF‐α/IL‐6/PGE2;PGE2DCs). However, the ability of vaccine DCs to induce a type 1‐polarized immune response in vivo probably relies on additional features, including their ability to induce a CXCR3‐dependent recruitment of NK cells into vaccine‐draining lymph nodes. Moreover, their guiding of rare tumour‐specific CD8+ T cells to sites of DC–CD4+ T cell interactions by secretion of CCL3 and CCL4 is needed. We therefore analysed the chemokine profile and the lymphocyte‐attracting ability in vitro of monocyte‐derived PGE2DCs and αDC1s from patients with CLL. αDC1s produced much higher levels of CXCR3 ligands (CXCL9/CXCL10/CXCL11) than PGE2DCs. Functional studies further demonstrated that αDC1s were superior recruiters of both NK and NKT cells. Moreover, αDC1s produced higher levels of CCL3/CCL4 upon CD40 ligation. These findings suggest that functional αDC1s, derived from patients with CLL, produce a desirable NK‐, NKT‐ and CD8+ T cell‐attracting chemokine profile which may favour a guided and Th1‐deviated priming of CD8+ T cells, supporting the idea that αDC1‐based vaccines have a higher immunotherapeutic potential than PGE2DCs.

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Vaccination with immature dendritic cells combined with CD40mAb induces protective immunity against B lymphoma in hu-SCID mice

Xiang

Zhang

2010

Biomedicine & Pharmacotherapy

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Dendritic cell-based immunogens for B-cell chronic lymphocytic leukemia

Cited by 8 publications

References 33 publications

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand�1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand�1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

Tumour‐loaded α‐type 1‐polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia Produce a Superior NK‐, NKT‐ and CD8⁺ T Cell‐attracting Chemokine Profile

Vaccination with immature dendritic cells combined with CD40mAb induces protective immunity against B lymphoma in hu-SCID mice

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Dendritic cell-based immunogens for B-cell chronic lymphocytic leukemia

Cited by 8 publications

References 33 publications

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand�1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

Lentivirus‑mediated RNA interference targeting programmed death receptor ligand�1 increases the immunologic anti‑tumor effect of dendritic cell vaccination against pancreatic cancer in SCID‑hu mice

Tumour‐loaded α‐type 1‐polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia Produce a Superior NK‐, NKT‐ and CD8+ T Cell‐attracting Chemokine Profile

Vaccination with immature dendritic cells combined with CD40mAb induces protective immunity against B lymphoma in hu-SCID mice

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Tumour‐loaded α‐type 1‐polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia Produce a Superior NK‐, NKT‐ and CD8⁺ T Cell‐attracting Chemokine Profile