Ig-Seq Analysis of tumor-infiltrating B cells (TIL-B) in a breast cancer mouse model

The adaptive immune system responds to the presence of foreign antigens by the activation of a highly complex defense mechanism consisting of two major arms: cellular immunity and humoral immunity. Yet, much of the focus in tumor immunology has been on the cellular immunity (cytotoxic CD8+ T cells), while B cells are increasingly being appreciated as crucial players in cancer therapies.

The advent of next-generation sequencing may allow a comprehensive characterization of the localized repertoire of tumor-reactive lymphocytes found in the tumor or in other compartments such as the bone marrow (BM), the blood, and the lymph node. This represents a unique opportunity to discover patient-specific, tumor-reactive cell repertoires, and to study their temporal dynamics and antitumor function.

We have characterized the antibody-repertoire derived from the Tumor-Infiltrating B cells using a breast cancer mouse model (4T1). Next-Generation Sequencing of B cells from four compartments (Tumor, Sentinel Lymph Node, BM, Blood) suggest that i) TIL-B cells encode antibodies that are a result of specific engagement with the tumor microenvironment ; ii) following tumor engagement, the TIL-B cells migrate to the bone marrow to become long-lived plasma cells and iii) TIL-B subsets consist an oligoclonal population which is highly polarized and is dominated by a small number of antibody clonotypes that are detected at low frequency in the bone marrow.