The Diagnostic, Prognostic, and Therapeutic Potential of Adaptive Immune Receptor Repertoire Profiling in Cancer

Abstract

Lymphocytes play a critical role in antitumor immune responses. They are directly targeted by some therapies, and the composition and spatial organization of intratumor T-cell populations is prognostic in some cancer types. A better understanding of lymphocyte population dynamics over the course of disease and in response to therapy is urgently needed to guide therapy decisions and to develop new therapy targets. Deep sequencing of the repertoire of antigen receptor-encoding genes expressed in a lymphocyte population has become a widely used approach for profiling the population's immune status. Lymphocyte antigen receptor repertoire deep sequencing data can be used to assess the clonal richness and diversity of lymphocyte populations; to track clone members over time, between tissues, and across lymphocyte subsets; to detect clonal expansion; and to detect the recruitment of new clones into a tissue. Repertoire sequencing is thus a critical complement to other methods of lymphocyte and immune profiling in cancer. This review describes the current state of knowledge based on repertoire sequencing studies conducted on human cancer patients, with a focus on studies of the T-cell receptor beta chain locus. The review then outlines important questions left unanswered and suggests future directions for the field.