Abstract 4046: Immune repertoire sequencing reveals tumor microenvironment and tracks clonally expanded B cell and T cell in blood

Abstract

Abstract The study of complex immunological diseases and tumor microenvironments has progressed through recent developments on sequencing of the immune repertoire. Using this approach, the interrogation of disease progression is facilitated through analysis of millions of V(D)J combinations from B cell antibodies (Igs) and T cell receptors (TCRs). One major challenge of immune repertoire sequencing is to accurately capture the structural and sequence complexities of antibodies and TCR genes. We have developed a method for accurate sequencing of full length immune gene repertoires of B cells and T cells. RNA extracted from tumor tissues containing tumor infiltrating lymphocytes, as well as matched peripheral blood mononuclear cells (PBMCs) were used to generate full length Ig and TCR libraries. Unique molecule index (UMI) was used to discretely barcode each mRNA molecule, enabling absolute quantitative ranking of antibody/TCR clone abundance. Full length immune repertoire sequencing facilitates detection of distinct and shared clones in tissue and blood samples, enabling identification of disease specific clones to evaluate immunotherapy effects. Highly expanded clones in tumor samples are also found in blood samples. RNA-seq libraries were also constructed from the same RNA for Ig and TCR libraries. The expression level of IGH/IGL/IGK and TRA/TRB in the immune sequencing libraries highly correlates with the RNA-seq data. In addition, both Ig and TCR libraries can be constructed in one tube to obtain a whole immune repertoire profile.Our immune repertoire sequencing approach allows accurate clonal determination for both Ig and TCR. This technique is applicable for investigation of lymphocytes infiltration of tumor microenvironments, tracing expanded B cell and T cells in blood samples, and monitoring of minimal residual disease. Citation Format: Chen Song, Pingfang Liu, Andrew Barry, Bradley W. Langhorst, Fiona J. Stewart, Salvatore Russello, Theodore B. Davis, Eileen T. Dimalanta. Immune repertoire sequencing reveals tumor microenvironment and tracks clonally expanded B cell and T cell in blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4046.