
종양 미세환경이 B세포 수용체(BCR) 레퍼토리의 특성에 미치는 영향을 체계적으로 분석하였다. 종양 침윤 B세포 레퍼토리는 주변 림프절 레퍼토리와 밀접하게 관련되어 있으며, 종양 침윤 B세포의 CDR-H3 특성은 말초혈액 B세포에 비해 덜 성숙하고 덜 특이적인 것으로 나타났다.


coremsg

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are thought to be significantly influenced by the tumor microenvironment in the form of secretory factors and biased cell-cell interactions. To address the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We show that draining LNs are differentially involved in the interaction with the tumor site and that there is significant heterogeneity even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations of intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of a BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the difference in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

### Competing Interest Statement

The authors have declared no competing interest.

*   (PBMC)
    :   Peripheral blood mononuclear cells
    (LN)
    :   lymph node
    ((tumor)-draining LNs)
    :   (tumor)-draining lymph nodes
    (BCR)
    :   B cell receptor
    (CDR-H3)
    :   complementarity-determining region 3 of a BCR heavy chain
    (TME)
    :   tumor microenvironment
    (SHM)
    :   somatic hypermutation
    (TLSs)
    :   tertiary lymphoid structures
    (TI-Bs)
    :   tumor-infiltrating B-cells
    (ADCC)
    :   antibody-dependent cytotoxicity
    (MDSC)
    :   myeloid-derived suppressor cells
    (LUAD)
    :   lung adenocarcinoma
    ( R apid A mplification of c DNA E nds)
    :   5’RACE
    (IGH)
    :   immunoglobulin heavy chain
    (SLE)
    :   systemic lupus erythematosus
    (CAR-T)
    :   chimeric antigen receptor T cell
    (MRCA)
    :   most recent common ancestor.

Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

암-환자의-종양-내부-및-주변-bcr-레퍼토리에-대한-체계적인-평가


암 환자의 종양 내부 및 주변 BCR 레퍼토리에 대한 체계적인 평가
