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Examining T Cells at Vaccine Sites of Tumor-bearing Hosts Provides Insights to Dysfunctional T-Cell Immunity

Barr, Kristen M.*,†,‡; Jing, Weiqing*,‡; Hallett, William H.D.§; Gershan, Jill A.*,‡; Johnson, Bryon D.*,†,‡

doi: 10.1097/CJI.0b013e318274590e
Basic Studies
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When tumor vaccines are administered as cancer immunotherapy, cellular interactions at the vaccine site are crucial to the generation of antitumor immunity. Examining interactions at the vaccine site could provide important insights to the success or failure of vaccination. Our laboratory previously showed that while administration of a cell-based vaccine to tumor-free mice leads to productive antineuroblastoma immunity, vaccination of tumor-bearing mice does not. The goal of this study was to examine immune effectors at the vaccine site to identify mechanisms responsible for the generation of ineffective antitumor immunity in tumor-bearing mice. The results of this study show that vaccine sites of tumor-bearing mice contained significantly fewer T cells than vaccine sites of tumor-free mice. Similar migration and proliferation of T cells was observed in the vaccine sites of tumor-bearing and tumor-free mice, but T cells in the sites of tumor-bearing mice were more apoptotic. T cells at the vaccine sites of both tumor-free and tumor-bearing mice had an effector-memory phenotype and expressed activation markers. Despite the activated phenotype, T cells from tumor-bearing mice elicited defective antitumor immune responses. Although T cells from vaccine sites of tumor-bearing mice were capable of producing inflammatory cytokines, the T cells from tumor-bearing mice produced lower levels of cytokines compared with T cells from the tumor-free mice. Remarkably, this defect seems to be systemic, affecting distal T cells in tumor-bearing mice. This study demonstrates that the defective vaccine-induced immune response to neuroblastoma in tumor-bearing hosts originates as a result of tumor burden, resulting in poor antitumor immunity.

*Department of Pediatrics, Section of Hematology-Oncology

Department of Microbiology, Medical College of Wisconsin

The Children’s Research Institute, Children’s Hospital of Wisconsin, Milwaukee

§Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI

Reprints: Bryon D. Johnson, Department of Pediatrics, Section of Hematology-Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. (e-mail: bjohnson@mcw.edu).

Received July 13, 2012

Accepted September 12, 2012

© 2013 Lippincott Williams & Wilkins, Inc.