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1032 Uncoupling CD39 and T cell antigen specificity in brain tumors
  1. Sierra Kleist,
  2. Shawn Musial,
  3. Hanna Degefu,
  4. Pamela Rosato and
  5. Jordan Isaacs
  1. Dartmouth College, Lebanon, NH, United States


Background Tumor-infiltrating lymphocytes have long been thought to encompass a repertoire recognizing primarily tumor antigens. However, our lab and others have found that tumor-infiltrating CD8+ T cells include a population with viral-specificity which can often outnumber tumor-reactive cells. Thus, identifying markers of tumor-reactive T cells are critical for developing ways to target this sub-population and boost anti-tumor immunity. Work to this end has defined CD39 and CD103 as putative markers of tumor-reactive T cells in several solid tumors. CD39+ CD8+ T cells have impaired cytokine production and increased expression of inhibitory receptors, while CD39- CD8+ T cells lack hallmarks of chronic antigen stimulation, highlighting their bystander role.

Methods In contrast, we unexpectedly found that CD39 is highly expressed on functional virus-specific CD8+ T cells in healthy brain compared to other non-lymphoid tissues examined. These findings prompted us to investigate whether the established CD39 antigen-specificity paradigm held true in brain tumors. To test this, we established a mouse model of glioblastoma (GBM) and melanoma brain metastasis harboring virus-specific memory T cells, similar to the observations found in humans.

Results Suprisingly, we found that CD39 expression was uniformly high on all CD8+ T cells in both brain tumor models, including on virus-specific T cells which also co-expressed CD103. Moreover, these CD39+ antiviral T cells remained functionally active and could mediate local inflammation upon recognition of cognate antigen. In contrast, in a mouse model of primary melanoma, bystander virus-specific T cells did not express CD39 while the bulk CD8+ population, including tumor-reactive T cells, expressed high CD39 as has been demonstrated clinically.

Conclusions Our ongoing studies aim to elucidate the functional role of CD39 in T-cell mediated immunity of brain tumors. Overall, these data suggest that CD39 may not stratify tumor-reactive CD8+ T cells in brain tumors as has been demonstrated in other solid tumors. Thus, therapeutic approaches to target CD39/CD103+ T cells or restore anti-tumor immunity through CD39 blockade may have different clinical implications in tumors of the central nervous system.

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