According to results of a study presented at the Society of Immunotherapy for Cancer (SITC) Annual Meeting 2019 in National Harbor, Maryland, a next-generation sequencing (NGS)-based approach was capable of simultaneously characterizing all 7 T- and B-cell receptor chains, and also provided potential predictors of treatment benefit in patients with renal cell carcinoma (RCC).
An extensive repertoire of T-cell and B-cell populations that expresses a wide range of antigen-specific receptors are at the heart of the adaptive immune system. More specifically, T- and B-cell receptor diversity is created through random recombination of variable (V), diversity (D), and joining (J) gene segments, or V and J gene segments alone. Hence, at any given point in time, the T-cell and B-cell repertoire in a single individual is represented by a huge number of different T- and B-cell clones or clonotypes.
Recently, high-throughput NGS has been used to profile the diversity of the T-cell and B-cell repertoire in individuals. One approach to this process involves RNA-based multiplex polymerase chain reaction (PCR) amplification of V-D-J or V-J gene segments, followed by high-throughput sequencing of the PCR amplicons, and subsequent bioinformatic interpretation of the reads obtained through NGS.
In this study, a novel quantitative PCR-based NGS technique was reported to allow for the simultaneous characterization of RNA associated with the loci of all 7 T- and B-cell receptors (ie, the alpha, beta, gamma, and delta chains of the T-cell receptor; and immunoglobulin (Ig)-K and Ig-L of the B-cell receptor) collected from both peripheral blood mononuclear cells (PBMCs) and formalin-fixed paraffin-embedded (FFPE) specimens from patients undergoing treatment for RCC.
Furthermore, this process was carried out as single reaction that circumvented the problem of PCR dimer artifacts.
Results of this study suggested that pretreatment diversity in T-cell receptor alpha and beta chains, as well as the B-cell to T-cell expression ratio, may be useful predictors of treatment response in patients with RCC.
Depinet M, Pan W, Wu S, et al. All-in-One, quantitative immune repertoire profiling of PBMC and FFPE for renal cancer treatment evaluation. Presented at the Society for Immunology of Cancer (SITC) Annual Meeting 2019. November 6-10, 2019. National Harbor, MD. Abstract P87.