Sixth Immunotherapy of Cancer conference (ITOC): advances and perspectives-a meeting report.

Immunotherapy has moved to the forefront of cancer treatment, illustrated by the accelerating pace of novel therapy approvals. In this complex environment, scientists rely on cutting edge conferences to stay informed. The Immunotherapy of Cancer (ITOC) conference was established jointly with the Society of the Immunotherapy of Cancer to bring the European researchers together.

Expression of MAC-1 (CD11b) in acute myeloid leukemia (AML) is associated with an unfavorable prognosis.

There is evidence to suggest, that cellular adhesion molecules and receptors could play a role in leukemia, e.g., through altered adhesive qualities of leukemic blasts.

Serum levels of CD137 ligand and CD178 are prognostic factors for progression of myelodysplastic syndrome.

Excess apoptosis leading to ineffective hematopoiesis is a common feature of myelodysplastic syndrome (MDS). CD178 (Fas ligand/APO-1 ligand) and CD137 ligand (CD137L), 2 molecules involved in the regulation of apoptosis, have previously been found in sera of patients with malignancies and have been hypothesized to participate in the pathogenesis of various diseases. We analyzed sera of patients with MDS and found that while time to progression of MDS correlated with the IPSS score there was no correlation of CD137L or CD178 serum levels with this score or with karyotype, bone marrow blast count or cytopenia.

Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer.

Purpose: Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). HPV-16 or -18 is commonly present in 70% of cervical cancers. HPV-positive tumor cells present antigens of the viral protein in the context of human leukocyte antigen (HLA) class I that can be recognized by CTLs.

Differentiation of promyelocytic leukaemia: alterations in Fas (CD95/Apo-1) and Fas ligand (CD178) expression.

The survival of leukaemic blasts contributes to the pathological mechanism of acute promyelocytic leukaemia (APL). While treatment of APL using retinoic acid (RA) is a model of differentiation therapy, little is known about possible effects of this treatment on the Fas/FasL system. Investigation of APL cells from patients undergoing differentiation therapy with RA and of promyelocytic HL-60 and monoblastic U-937 cells cultured with RA revealed a reduction of surface expression of both Fas and its ligand.

Modulation of apoptosis by mitochondrial uncouplers: apoptosis-delaying features despite intrinsic cytotoxicity.

Disruption of mitochondrial electron transport and opening of the so-called mitochondrial permeability transition pores (PTPs) are early events in apoptotic cell death and may be caused by the uncoupler of mitochondrial oxidation and phosphorylation, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). We investigated the cellular toxicity of FCCP in HL60 and CCRF-CEM cells alone or in combination with the known apoptosis inducers such as inhibitor of serine/threonine protein kinases staurosporine (Sts) and protein kinase C inhibitor chelerythrine. FCCP induced apoptotic cell death in both cell lines in a dose-dependent manner, and we were able to demonstrate an appearance of caspase-3-dependent PARP cleavage fragments with Western blot and the appearance of large (15-50 kb) DNA fragments using pulsed-field gel electrophoresis.