Neuroblastoma and Glioblastoma Cases With Amplified Oncogenes Have Reduced Numbers of Tumor-Resident Adaptive Immune Receptor Recombinations.

Abstract

In certain cancers, oncogene amplification is correlated with an immunologically cold or noninflamed, tumor immune microenvironment (TIME) and a worse prognosis, for example, in the case of MYCN-amplified neuroblastoma (NBL). However, for other cancer types, the relationship between oncogene amplification and immune response is more complicated or unresolved. One such cancer is glioblastoma multiforme (GBM), in which the epidermal growth factor receptor (EGFR) oncogene is commonly amplified. Unlike MYCN-amplified NBL, EGFR-amplified GBM has not been shown to correlate with a distinct survival probability. Given this contrasting state for NBL and GBM, we sought to apply a genomics approach to evaluating the immune response for cases with gene amplification. Our results confirmed and added further specificity to the cold TIME of MYCN-amplified NBL. Moreover, we demonstrated a novel state of immunologically cold EGFR-amplified GBM tumors. This approach to using copy number variation and immune receptor recombination read recovery levels to assess gene amplification and TIME, respectively, may be particularly efficient for the rapid evaluation of many other cancer types.