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- W4313368536 abstract "Abstract The presence of CD8 T cells in tumors, including melanomas, is correlated with longer survival. Cutaneous melanoma is a highly immunogenic malignancy with high rate of dissemination into central nervous system but the brain is considered immunologically privileged due to the blood-brain barrier, which limits T cell entry. To determine if brain tumors are also poorly infiltrated by T cells we evaluated intracranial (IC) and subcutaneous (SC) B16 melanomas expressing different model antigens. CD8 T cells were present in IC tumors 7 days post tumor implantation in B16 melanomas expressing chicken ovalbumin (B16OVA) or influenza M1 protein (B16M1), but infiltrates were only 10% of those observed in SC tumors. We also observed that expression of homing receptor ligands (HRLs) known to mediate T cell infiltration was lower on IC than SC tumor-associated vasculature. Despite the fact that HRL expression decreased over time in tumors grown in both locations, T cell infiltrates increased, suggesting that HRL are not the only factor limiting T cells entry into IC tumors. To determine whether the IC tumor infiltrate size was limited by inefficient stimulation of effectors cells, we vaccinated mice to generate fully activated effector T cells able to recognize tumor associated antigen. Vaccination normalized the infiltrate sizes in IC and SC tumors. Interestingly, this was also dependent on expression of Ag by the tumor cells. This suggests that IC tumors are not able to efficiently elicit a robust immune response, possibly due to limitations on drainage to lymph nodes, while IC tumor vasculature does not impose inherently greater limitations on the ability of T cells to enter." @default.
- W4313368536 created "2023-01-06" @default.
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- W4313368536 date "2020-05-01" @default.
- W4313368536 modified "2023-09-27" @default.
- W4313368536 title "Low immunogenicity of intracranial tumors limits immune response to brain malignancies" @default.
- W4313368536 doi "https://doi.org/10.4049/jimmunol.204.supp.242.51" @default.
- W4313368536 hasPublicationYear "2020" @default.
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