Malignant gliomas are lethal
brain tumors for which novel
therapies are urgently needed. In animal models, vaccination with
tumor-associated Ags efficiently primes T cells to clear
gliomas. In clinical trials,
cancer vaccines have been less effective at priming T cells and extending survival. Generalized immune suppression in the
tumor draining lymph nodes has been documented in multiple
cancers. However, a systematic analysis of how vaccination at various distances from the
tumor (closest to farthest) has not been reported. We investigated how the injection site chosen for vaccination dictates CD8 T cell priming and survival in an OVA-transfected murine
glioma model.
Glioma-bearing mice were vaccinated with
Poly:ICLC plus OVA
protein in the neck, hind leg, or foreleg for drainage into the cervical, inguinal, or axillary lymph nodes, respectively. OVA-specific CD8 T cell number, TCR affinity, effector function, and infiltration into the brain decreased as the vaccination site approached the
tumor. These effects were dependent on the presence of the
tumor, because injection site did not appreciably affect CD8 T cell priming in
tumor-free mice. Our data suggest the site of vaccination can greatly impact the effectiveness of
cancer vaccines. Considering that previous and ongoing clinical trials have used a variety of injection sites, vaccination site is potentially a critical aspect of study design that is being overlooked.