0000000000484992
AUTHOR
Emmanuel Katsanis
PIAS1 and STAT-3 impair the tumoricidal potential of IFN-γ-stimulated mouse dendritic cells generated with IL-15
Primarily defined by their antigen-presenting property, dendritic cells (DCs) are being implemented as cancer vaccines in immunotherapeutic interventions. DCs can also function as direct tumor cell killers. How DC cytotoxic activity can be efficiently harnessed and the mechanisms controlling this nonconventional property are not fully understood. We report here that the tumoricidal potential of mouse DCs generated from myeloid precursors with GM-CSF and IL-15 (IL-15 DCs) can be triggered with the Toll-like receptor (TLR) 4 ligand lipopolysaccharide to a similar extent compared with that of their counterparts, conventionally generated with IL-4 (IL-4 DCs). The mechanism of tumor cell killing…
Immunologic effects of rituximab on the human spleen in immune thrombocytopenia
Abstract Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell de…
Abstract 4740: Doxorubicin eliminates tumor-induced myeloid-derived suppressor cells and enhances T-helper lymphocyte-based immunotherapy in a murine breast cancer model.
Abstract Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of cells equipped with the ability to inhibit T lymphocyte-mediated immune responses. A significant increase in the number of MDSC has been reported in the blood, secondary lymphoid organs and tumor beds in tumor-bearing animals and in patients with many types of cancers. MDSC frequency correlates with the disease stage and prognosis. These cells impair CD8+ cytotoxic T lymphocyte (CTL)-mediated anti-tumor immunity by different overlapping mechanisms such as reactive oxygen species or immunosuppressive cytokine production. Importantly, MDSC elimination or inactivation substantially enhances the efficiency …
Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia
AbstractTherapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4+ T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4+CD25+FoxP3+ regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3+ Tregs from naive CD4+CD25−FoxP3− T cells by an interferon-γ–dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with …