Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer.
A fluorescence-based, high-resolution imaging approach was used to visualize longitudinally the cellular events unfolding during T cell-mediated tumor destruction. The dynamic interplay of T cells, cancer cells, cancer antigen loss variants, and stromal cells-all color-coded in vivo-was analyzed in established, solid tumors that had developed behind windows implanted on the backs of mice. Events could be followed repeatedly within precisely the same tumor region-before, during and after adoptive T cell therapy-thereby enabling for the first time a longitudinal in vivo evaluation of protracted events, an analysis not possible with terminal imaging of surgically exposed tumors. T cell infiltration, stromal interactions, and vessel destruction, as well as the functional consequences thereof, including the elimination of cancer cells and cancer cell variants were studied. Minimal perivascular T cell infiltrates initiated vascular destruction inside the tumor mass eventually leading to macroscopic central tumor necrosis. Prolonged engagement of T cells with tumor antigen-crosspresenting stromal cells correlated with high IFNγ cytokine release and bystander elimination of antigen-negative cancer cells. The high-resolution, longitudinal, in vivo imaging approach described here will help to further a better mechanistic understanding of tumor eradication by T cells and other anti-cancer therapies.
Department of Pathology; The University of Chicago; Chicago, IL USA.
Andrea
A
Schietinger
Department of Pathology; The University of Chicago; Chicago, IL USA.
Ainhoa
A
Arina
Department of Pathology; The University of Chicago; Chicago, IL USA.
Rebecca B
RB
Liu
Department of Physiology and Biophysics; Vanderbilt University School of Medicine; Nashville, TN USA.
Sam
S
Wells
Department of Radiation Oncology and The Vanderbilt-Ingram Cancer Center; Vanderbilt University School of Medicine; Nashville, TN USA.
Jianhua
J
Huang
Department of Pathology; The University of Chicago; Chicago, IL USA.
Boris
B
Engels
Integrated Microscopy Core; The University of Chicago; Chicago, IL USA.
Vytas
V
Bindokas
Department of Immunology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.
Todd
T
Bartkowiak
School of Medicine; The University of Chicago; Chicago, IL USA.
David
D
Lee
Departments of Cancer Immunotherapeutics & Tumor Immunology; City of Hope; Duarte, CA USA.
Andreas
A
Herrmann
Department of Physiology and Biophysics; Vanderbilt University School of Medicine; Nashville, TN USA.
David W
DW
Piston
Center for Systems Biology; Massachusetts General Hospital and Harvard Medical School; Boston, MA USA.
Mikael J
MJ
Pittet
Department of Radiation Oncology and The Vanderbilt-Ingram Cancer Center; Vanderbilt University School of Medicine; Nashville, TN USA ; Center for Cancer Research; National Cancer Institute, NIH; Frederick, MD USA.
P Charles
PC
Lin
Department of Immunology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.
Tomasz
T
Zal
Department of Pathology; The University of Chicago; Chicago, IL USA.
Hans
H
Schreiber
CD8 T cell; cancer; imaging; stroma; tumor immunology; tumor microenvironment