Distribution of adoptively transferred, tumor-sensitized lymphocytes in the glioma-bearing rat.
For adoptively transferred lymphocytes to exert anti-tumor effects in vivo, they must traffic or initiate the migration of endogenous immune cells to the site of tumor. Using a rat model, we examined the trafficking of tumor-sensitized lymphocytes to an intracerebral glioma. By labeling the cells with 111Indium oxine (111In) prior to intravenous injection, we were able to quantify the relative number of lymphocytes that traveled to the tumor site. There was no difference in lymphocytic influx between the tumor-bearing and non-tumor-bearing cerebral hemispheres in 3-day rat glioma models. However, in 7-day models, significantly greater numbers of 111In-labeled lymphocytes resided in the tumor-bearing hemisphere at 12 h post-administration. This number increased more than two-fold by 24 h post-adoptive transfer. Using fluorescent-labeled lymphocytes and microscopy, we confirmed that the detection of radioactivity within the brain was truly due to tumor infiltrating 111In-labeled lymphocytes. Adoptively transferred cells were found in perivascular and peritumoral locations. These data demonstrate that tumor-sensitized lymphocytes traffic to an intracerebral target site where they can exert an effect, further supporting adoptive immunotherapy as a treatment for glioma.
Hazelrigg
Monica R
MR
Department of Anatomy, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA 23298-0631, USA.
Hirsch
Jerry I
JI
Merchant
Randall E
RE
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000166:cytology / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D002465:Cell Movement / Q000276:immunology; D005260:Female; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344