Exploiting adaptive immune receptor recombination read recoveries from exome files to identify subsets of ALL and to establish TCR features that correlate with better outcomes.

Abstract

The recovery of adaptive immune receptor (IR) recombination reads from tumour-derived genomics files has advanced the understanding of the immune system's interaction with cancer. This approach has been largely limited to solid tumours, where genomics file preparation allows for the recovery of adaptive IR reads corresponding to the T-cells and B-cells found in the solid tumour microenvironment. In this study, we sought to determine whether IR recombination reads from liquid tumour genomics files could also be informative. We recovered the adaptive IR recombination reads from acute lymphoblastic leukaemia (ALL) normal and pathological genomics files of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-ALL, phase 2 project. In the bone marrow setting, results indicated that there was little or no B-cell response to ALL. However, results did show survival distinctions for B-cell ALL, in cases with specific T-cell complementarity determining region-3 chemical features, potentially reflecting specificity of the adaptive T-cell response against ALL. Furthermore, we found that the B-cell form of ALL, as well as what is likely TRD clonotypic, T-cell ALL, could likely be diagnosed via the recovery of B-cell receptor and TRD recombination reads, respectively, from pathological bone marrow exome files. Recovery of IR recombination reads from ALL exomes could aid in sub-type diagnoses and prognoses.