High-throughput sequencing of the immune repertoire in oncology: Applications for clinical diagnosis, monitoring, and immunotherapies

摘要

Abstract The diagnostic, monitoring and therapeutic options for cancers currently remain limited. These limitations represent a large threat to human health. Adaptive immunity, which is dependent on diverse repertoires of B cell receptors (BCRs) and T cell receptors (TCRs), plays a critical role in the anti-tumor immune response. Modulation and surveillance of adaptive immunity has become a powerful weapon to combat cancers. Recently, the high-throughput sequencing of immune repertoire (HTS-IR) technology, which provides a robust tool for deep sequencing repertoires of BCRs or TCRs, has been applied in the development of tumor biomarkers and immunotherapeutics for cancers. This review will first provide an overview of the advancement of HTS-IR technology at the population-cell and single-cell levels. It will then provide a current summary of the applications of HTS-IR technology in the diagnosis and monitoring of minimal residual disease (MRD), focusing on immune reconstitution after the treatment of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in B/T-cell malignancies, and the precise detection of tumor-infiltrating lymphocytes (TILs) in non-B/T-cell malignancies. Finally, current advances of HTS-IR technology in cancer immunotherapeutic applications, such as therapeutic antibodies, CAR-T cell based-adoptive immunotherapies, and neoantigen-specific TCR-T cell-based adoptive immunotherapies, will be introduced. Highlights ? Stepwise V(D)J recombination mainly contributes to the repertoires of the B-cell receptor (BCR) or T-cell receptor (TCR). ? HTS-IR technology allows a high-resolution and panoramic analysis of B- or T-cell repertoires at population- or single-cell level. ? HTS-IR technology has been applied for the identification and development of prognostic and therapeutic tumor biomarkers. ? Application of HTS-IR in therapeutic antibodies, CAR-T or neoantigen-specific TCR-T cell-based adoptive immunotherapy.