Lymphocyte activation gene-3 (LAG-3, CD223) in plasmacytoid dendritic cells (pDCs): a molecular target for the restoration of active antitumor immunity

Chiara Castelli; Frédéric Triebel; Licia Rivoltini; Chiara Camisaschi

doi:10.4161/21624011.2014.967146

Lymphocyte activation gene-3 (LAG-3, CD223) in plasmacytoid dendritic cells (pDCs): a molecular target for the restoration of active antitumor immunity

Oncoimmunology. 2014 Dec 21;3(11):e967146. doi: 10.4161/21624011.2014.967146. eCollection 2014 Nov.

Authors

Chiara Castelli¹, Frédéric Triebel², Licia Rivoltini¹, Chiara Camisaschi¹

Affiliations

¹ Unit of Immunotherapy of Human Tumors; Dept. of Experimental Oncology and Molecular Medicine; Fondazione IRCCS Istituto Nazionale dei Tumori ; Milano, Italy.
² Immutep S.A.; Faculté de Pharmacie; Chatenay-Malabry ; France.

Abstract

We have recently reported that lymphocyte activation gene-3 (LAG-3,CD223) mediates the alternative, IFNα-deficient activation of plasmacytoid dendritic cells (pDCs) at tumor sites. Our findings define a novel tumor-driven strategy that promotes immunosuppression by pDCs, and we have provided more detailed information regarding the immunomodulatory role of of LAG-3. The translational relevance of our results for the treatment of tumors and autoimmune diseases is discussed herein.

Keywords: ADCC, antibody-dependent cell cytotoxicity; APCs, antigen-presenting cells; DDCs, dermal dendritic cells; IMP-321; LAG-3, lymphocyte activation gene-3; LNs, lymph nodes; MDSCs, myeloid-derived suppressor cells; PD-1, programmed cell death 1; TLRs, toll-like receptors; Tregs, regulatory T cells.; lymphocyte activation gene-3 (LAG-3); mAbs, monoclonal antibodies; melanoma; pDCs, plasmacytoid dendritic cells; plasmacytoid dendritic cells (pDCs); psoriasis.