title: Visualizing the dynamic of adoptively transferred T cells during the rejection of large established tumors.
abstract: Adoptive T-cell therapy (ATCT) can result in tumor rejection, yet the behavior and fate of the introduced T cells remain unclear. We developed a novel bioluminescence mouse model, which enabled highly sensitive detection of T-cell signals at the single-cell level. Transferred T cells preferentially accumulated within antigen-positive tumors, relative to the unaffected areas in each mouse, and remarkably, expanded within both lymphopenic and P14 mice. This expansion was controlled and efficient, as evaluated by bioluminescence imaging (BLI) of the T-cell signals and by tumor rejection respectively. Analysis of the population dynamics of transferred T cells in ATCT of large tumors revealed that proliferation did not always follow a simple linear pattern of expansion, but showed an oscillating pattern of expansion and contraction that was often followed by a rebound, until full tumor rejection was achieved. Furthermore, visualizing the recall response showed that the transferred T cells responded expeditiously, indicating the ability of these cells to survive, establish memory and compete with endogenous T cells for as long as 1 year after rejecting the tumor.
authors: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. j.charo@mdc-berlin.de
authors: Jehad
authors: J
authors: Charo
authors: Cynthia
authors: C
authors: Perez
authors: Christian
authors: C
authors: Buschow
authors: Ana
authors: A
authors: Jukica
authors: Melinda
authors: M
authors: Czeh
authors: Thomas
authors: T
authors: Blankenstein
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002469:Cell Separation; D017690:Cell Transplantation / Q000379:methods; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D016219:Immunotherapy, Adoptive / Q000379:methods*; D049410:Luciferases, Renilla / Q000235:genetics; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology*; D013601:T-Lymphocytes / Q000637:transplantation*
chemical_list: D049410:Luciferases, Renilla