Immune repertoire: A potential biomarker and therapeutic for hepatocellular carcinoma.

The immune repertoire (IR) refers to the sum of B cells and T cells with functional diversity in the circulatory system of one individual at any given time. Immune cells, which reside within microenvironments and are responsible for protecting the human body, include T cells, B cells, macrophages, and dendritic cells. These dedicated immune cells have a characteristic structure and function. T and B cells are the main lymphocytes and are responsible for cellular immunity and humoral immunity, respectively. The T cell receptor (TCR) and B cell receptor (BCR) are composed of multiple peptide chains with antigen specificity. The amino acid composition and sequence order are more diverse in the complementarity-determining regions (including CDR1, CDR2 and CDR3) of each peptide chain, allowing a vast library of TCRs and BCRs. IR research is becoming increasingly focused on the study of CDR3 diversity. Deep profiling of CDR3s using high-throughput sequencing is a powerful approach for elucidating the composition and distribution of the CDR3s in a given sample, with in-depth information at the sequence level. Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. To identify novel biomarkers for diagnosis and drug targets for therapeutic interventions, several groups attempted to describe immune repertoire characteristics of the liver in the physiological environment or/and pathological conditions. This paper reviews the recent progress in IR research on human diseases, including hepatocellular carcinoma, attempting to depict the relationships between hepatocellular carcinogenesis and the IR, and discusses the possibility of IR as a potential biomarker and therapeutic for hepatocellular carcinoma.

Han Y ，Li H ，Guan Y ，Huang J ... -  《-》

Clonal distribution and intratumour heterogeneity of the B-cell repertoire in oesophageal squamous cell carcinoma.

Recent successes in tumour immunotherapies have highlighted the importance of tumour immunity. However, most previous studies to date have focused on T-cell immune response, although B cells are key players in the core immune network and are associated with T-cell immune response. Based on our previous study delineating T-cell receptor (TCR) repertoire in seven patients with oesophageal squamous cell carcinoma (ESCC), this study profiled the B-cell receptor (BCR) repertoire of multiple tumour regions, adjacent normal tissue, and blood from the same seven patients to reveal the characteristics of B-cell immunity and the relationship to TCR repertoire in ESCC patients. We found that intratumour BCR repertoire was significantly more oligoclonal than matched adjacent normal tissue or peripheral blood and, moreover, clonal amplification of B cells in multiple tumour regions was significantly heterogeneous, although clonal amplification of the TCR repertoire across different tissue compartments and regions of the same tumour was similar. However, both BCR and TCR repertoires in the tumour microenvironment were distinct from those in adjacent normal tissues and blood, and thus represented a group of B and T cells that were spatially confined to the tumour microenvironment and could react to tumour antigens. Additionally, B- and T-cell clones varying between different tumour regions showed intratumour heterogeneity of B- and T-cell immune response. Thus, multiple tumour biopsies could be essential to comprehensively delineate the adaptive immune response to an individual ESCC. These findings expand our understanding of adaptive anti-tumour immunity and shed more light on ESCC immunotherapy. This study provides insights into the intratumour heterogeneity of the BCR repertoire as well as the difference and relationship between the BCR and TCR repertoire in ESCC, expanding our understanding of adaptive anti-tumour immunity and ESCC immunotherapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Zhang C ，Huang H ，Miao Y ，Xiong H ，Lu Z ... -  《-》

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

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.

Ye B ，Smerin D ，Gao Q ，Kang C ，Xiong X ... -  《-》

Current status and recent advances of next generation sequencing techniques in immunological repertoire.

Hou XL ，Wang L ，Ding YL ，Xie Q ，Diao HY ... -  《-》

Profiling the TRB and IGH repertoire of patients with H5N6 Avian Influenza Virus Infection by high-throughput sequencing.

Peng W ，Liu S ，Meng J ，Huang J ，Huang J ，Tang D ，Dai Y ... -  《Scientific Reports》