Lymphocyte migration and retention properties affected by ibrutinib in chronic lymphocytic leukemia.

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is widely used for treatment of patients with relapsed/refractory or treatment-naïve chronic lymphocytic leukemia (CLL). A prominent effect of ibrutinib is to disrupt the retention of CLL cells from supportive lymphoid tissues, by altering BTK-dependent adhesion and migration. To further explore the mechanism of action of ibrutinib and its potential impact on non-leukemic cells, we quantified multiple motility and adhesion parameters of human primary CLL cells and non-leukemic lymphoid cells.

Stochastic asymmetric repartition of lytic machinery in dividing CD8 T cells generates heterogeneous killing behavior.

Cytotoxic immune cells are endowed with a high degree of heterogeneity in their lytic function, but how this heterogeneity is generated is still an open question. We therefore investigated if human CD8 T cells could segregate their lytic components during telophase, using imaging flow cytometry, confocal microscopy, and live-cell imaging. We show that CD107a-intracellular vesicles, perforin, and granzyme B unevenly segregate in a constant fraction of telophasic cells during each division round.

Multiparametric analysis of CD8 T cell compartment phenotype in chronic lymphocytic leukemia reveals a signature associated with progression toward therapy.

CD8 T cells are frontline defenders against cancer and primary targets of current immunotherapies. In CLL, specific functional alterations have been described in circulating CD8 T cells, yet a global view of the CD8 T cell compartment phenotype and of its real impact on disease progression is presently elusive. We developed a multidimensional statistical analysis of CD8 T cell phenotypic marker expression based on whole blood multi-color flow-cytometry.

Individual Human Cytotoxic T Lymphocytes Exhibit Intraclonal Heterogeneity during Sustained Killing.

The killing of antigen-bearing cells by clonal populations of cytotoxic T lymphocytes (CTLs) is thought to be a rapid phenomenon executed uniformly by individual CTLs. We combined bulk and single-CTL killing assays over a prolonged time period to provide the killing statistics of clonal human CTLs against an excess of target cells. Our data reveal efficiency in sustained killing at the population level, which relied on a highly heterogeneous multiple killing performance at the individual level.

A biased competition theory of cytotoxic T lymphocyte interaction with tumor nodules.

The dynamics of the interaction between Cytotoxic T Lymphocytes (CTL) and tumor cells has been addressed in depth, in particular using numerical simulations. However, stochastic mathematical models that take into account the competitive interaction between CTL and tumors undergoing immunoediting, a process of tumor cell escape from immunesurveillance, are presently missing. Here, we introduce a stochastic dynamical particle interaction model based on experimentally measured parameters that allows to describe CTL function during immunoediting.

Selection of biologically relevant genes with a wrapper stochastic algorithm.

We investigate an important issue of a meta-algorithm for selecting variables in the framework of microarray data. This wrapper method starts from any classification algorithm and weights each variable (i.e.