Systemic Adaptive Immune Parameters Associated with Neuroblastoma Outcomes: the Significance of Gamma-Delta T Cells

Abstract

We mined a set of neuroblastoma (NBL) exomes for immune receptor recombinations representing all seven, human adaptive immune receptor genes, using a very high standard for identifications of V- and J-gene segments in sequencing reads. Results indicated an unusually large number of TRD recombination reads in the NBL samples, possibly related to the younger age of the patients. In general, recovery of immune receptor (IR) recombination reads representing any of the immune receptors, from either blood or tumor samples, was associated with a lower overall survival rate, consistent with an emerging literature indicating that systemic immunology parameters can be informative for cancer evaluations. Despite the overall negative association of IR recombination frequencies and outcomes, survival rate distinctions could still be established as associated with certain chemical features of IR complementarity determining region-3 (CDR3) amino acid sequences, thereby likely revealing a distinction between the negative impacts of a general adaptive immune response versus the positive aspects of specific CDR3 chemical interaction potentials. These data underscore the relevance of gamma-delta T cells in the development of cancer in younger patients. And for the first time, these data allow a distinction within an NBL cohort with active disease, between two contrasting systemic immune states: (i) general and likely harmful adaptive immunity development versus (ii) a likely positive, adaptive immune response with particular antigenic specificities.