In the last years, a new human subset of blood/tissue proinflammatory dendritic cells, called "slanDCs",
has been identified, whose function in diseases is not completely known. In such regard, our group has recently
demonstrated that slanDCs infiltrate metastatic tumor-draining lymph nodes in carcinoma patients .
Moreover, our preliminary results suggest that slanDCs also infiltrate diffuse large B cell lymphomas (DLBCL),
whose "standard of care" therapy consists of antiblastic drugs in association with Rituximab (RTX). RTX is a
monoclonal antibody that targets CD20 in B cells mediating an antibody dependent cellular cytotoxicity
(ADCC) involving NK cells via the engagement of their CD16/FcγRIII. Since also slanDCs express CD16, it is
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plausible that they may contribute to the global effect of RTX-mediated ADCC observed in DLBCL patients.
The latter might be very relevant at the light of their localization in strict contact with tumor B cells
(unpublished observations). Aim of this proposal is to elucidate whether slanDCs are involved in RTXmediated
ADCC in DLBCL patients and how important they are. To pursue these objectives, our study will
be articulated into the following tasks (WP). We will: asses the capacity/extent of RTX-mediated ADCC toward
B cells by blood slanDCs from healthy donors, comparing them to those by NK cells and other CD16+
leukocytes (WP1); ii) identify potential effector mechanism(s) whereby slanDCs exert RTX-mediated
elimination of B cells (WP2); iii) evaluate whether circulating slanDCs and lymphoma-infiltrating slanDCs
from DLBCL patients are phenotypically/functionally altered and exert RTX-mediated ADCC or RTX-mediated
phagocytosis similarly to circulating slanDCs from healthy donors (WP3); iv) investigate whether blood, as well
as nodal slanDC content and phenotype, correlate with DLBCL therapy outcome (WP4). Altogether, results
from this study will provide novel information on the role of slanDCs in cancer.