Type 1-polarized dendritic cells loaded with autologous tumor are a potent immunogen against chronic lymphocytic leukemia

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Journal of Leukocyte Biology, doi:10.1189/jlb.1107737

Type 1-polarized dendritic cells loaded with autologous tumor are a potent

immunogen against chronic lymphocytic leukemia

Je-Jung Lee , A. Foon , Robbie B. Mailliard , Ravikumar Muthuswamy , and

Pawel Kalinski @

Departments of Surgery and Medicine, University of Pittsburgh, University of

Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA

@ To whom correspondence should be addressed. E-mail: kalinskip@... .

Abstract

Induction of active tumor-specific immunity in patients with chronic lymphocytic

leukemia (CLL) and other hematologic malignancies is compromised by the deficit

of endogenous dendritic cells (DCs). In attempt to develop improved vaccination

strategies for patients with CLL and other tumors with poorly identified

rejection antigens, we tested the ability of ex vivo-generated DCs to

cross-present the antigens expressed by CLL cells and to induce CLL-specific,

functional CTL responses. Monocyte-derived DCs from CLL patients were induced to

mature using a " standard " cytokine cocktail (in IL-1, TNF-, IL-6, and PGE2) or

using an -type 1-polarized DC (DC1) cocktail (in IL-1, TNF-, IFN-, IFN-, and

polyinosinic:polycytidylic acid) and were loaded with -irradiated, autologous

CLL cells. DC1 from CLL patients expressed substantially higher levels of

multiple costimulatory molecules (CD83, CD86, CD80, CD11c, and CD40) than

standard DCs (sDCs) and immature DCs, and their expression of CCR7 showed

intermediate level. DC1 secreted substantially higher (10-60 times) levels of

IL-12p70 than sDCs. Although DC1 and sDCs showed similar uptake of CLL cells,

DC1 induced much higher numbers (range, 2.4-38 times) of functional CD8+ T cells

against CLL cells. The current demonstration that autologous tumor-loaded DC1

are potent inducers of CLL-specific T cells helps to develop improved

immunotherapies of CLL.