Precision immunophenotyping by high-throughput TCR sequencing in human glioma

Immunotherapy for glioblastoma (GBM) is the subject of numerous clinical trials, given the potential for the adaptive immune response to combat this diffusely infiltrating tumor. However, rational application of immunotherapy to these tumors is challenging because of the peculiar immune privilege of the brain and the molecular heterogeneity of glioma antigens. Little is known about patient-to-patient variability in the potential to generate anti-glioma immune responses of their systemic and local T cell populations. We conducted a foundational study of the populationwide characteristics of both the peripheral blood and local, tissue-infiltrating T lymphocytes (TILs) of glioma patients using TCRseq. Through reverse transcription and pan-repertoire amplification of the TCR-alpha and -beta chains we generated TCRseq libraries from matched surgical tissue and peripheral blood cells. Using peripheral blood samples from primary GBM, low-grade glioma, and non-tumor patients (N=14), we define new immunophenotypes using statistical metrics based on