Patient-individualized CD8+cytolytic T-cell therapy effectively combats minimal residual leukemia in immunodeficient mice

Adoptive transfer of donor-derived cytolytic T-lymphocytes (CTL) has evolved as a promising strategy to improve graft-versus-leukemia (GvL) effects in allogeneic hematopoietic stem-cell transplantation. However, durable clinical responses are often hampered by limited capability of transferred T cells to establish effective and sustained antitumor immunity in vivo. We therefore analyzed GvL responses of acute myeloid leukemia (AML)-reactive CD8(+) CTL with central and effector memory phenotype in a new allogeneic donor-patient specific humanized mouse model. CTL lines and clones obtained upon stimulation of naive CD45RA(+) donor CD8(+) T cells with either single HLA antigen-mismatched or HL…

Patterns of oncogene co-expression at single cell resolution in cancer influence survival

AbstractBackgroundCancers often overexpress multiple clinically relevant oncogenes. However, it is not known if multiple oncogenes within a cancer combine uniquely in specific cellular sub-populations to influence clinical outcome. We studied this phenomenon using the prognostically relevant oncogenes MYC, BCL2 and BCL6 in Diffuse Large B-Cell Lymphoma (DLBCL).MethodsQuantitative multispectral imaging simultaneously measured oncogene co-expression at single-cell resolution in reactive lymphoid tissue (n=12) and four independent cohorts (n=409) of DLBCL. Mathematically derived co-expression phenotypes were evaluated in DLBCLs with immunohistochemistry (n=316) and eight DLBCL cohorts with gen…

MYC, BCL2 AND BCL6 COEXPRESSION PATTERNS AT SINGLE‐CELL RESOLUTION RE‐DEFINE DOUBLE EXPRESSOR LYMPHOMAS

Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion

Activation of TNFR2 with a novel agonist expands T reg cells in vivo and protects allo-HCT recipients from acute GvHD while sparing antilymphoma and antiinfectious properties of transplanted donor T cells.

Lack of NFATc1 SUMOylation prevents autoimmunity and alloreactivity

A novel transgenic mouse, in which the transcription factor NFATc1 bears lysine-to-arginine mutations that prevent modification by SUMO, develops normally and is healthy. However, SUMO-insensitive NFATc1 transmits strong tolerogenic signals, thus preventing autoimmune and alloimmune T cell responses.