Carcinogenesis in the process of long-term co-evolution of tumor cells and immune environment essentially becomes possible due to incorrect decisions made, remembered, and reproduced by the immune system at the level of clonal populations of antigen-specific T- and B-lymphocytes. Tumor-immunity interaction determines the nature of such errors and, consequently, delineates the possible ways of successful immunotherapeutic intervention. It is generally recognized that tumor-infiltrating B cells (TIL-B) can play both pro-tumor and anti-tumor roles. However, the exact mechanisms that determine the contribution of clonal B cell lineages with different specificities and functions remain largely unclear. This is due to the variability of cancer types, the molecular heterogeneity of tumor cells, and, to a large extent, the individual pattern of each immune response. Further progress requires detailed investigation of the functional properties and phenotypes of clonally heterogeneous B cells in relation to their antigenic specificities, which determine the functionality of both effector B lymphocytes and immunoglobulins produced in the tumor environment. Based on a real understanding of the role of clonal antigen-specific populations of B lymphocytes in the tumor microenvironment, we need to learn how to develop new methods of targeted immunotherapy, as well as adapt existing treatment options to the specific needs of different patients and patient subgroups. In this review, we will cover B cells functional diversity and their multifaceted roles in the tumor environment.
- MeSH
- B-lymfocyty MeSH
- CD8-pozitivní T-lymfocyty * MeSH
- imunoterapie MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory * terapie metabolismus MeSH
- tumor infiltrující lymfocyty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Our current understanding of whether B cell involvement in the tumor microenvironment benefits the patient or the tumor - in distinct cancers, subcohorts and individual patients - is quite limited. Both statements are probably true in most cases: certain clonal B cell populations contribute to the antitumor response, while others steer the immune response away from the desired mechanics. To step up to a new level of understanding and managing B cell behaviors in the tumor microenvironment, we need to rationally discern these roles, which are cumulatively defined by B cell clonal functional programs, specificities of their B cell receptors, specificities and isotypes of the antibodies they produce, and their spatial interactions within the tumor environment. Comprehensive analysis of these characteristics of clonal B cell populations is now becoming feasible with the development of a whole arsenal of advanced technical approaches, which include (1) methods of single-cell and spatial transcriptomics, genomics, and proteomics; (2) methods of massive identification of B cell specificities; (3) methods of deep error-free profiling of B cell receptor repertoires. Here we overview existing techniques, summarize their current application for B cells studies and propose promising future directions in advancing B cells exploration.
- MeSH
- B-lymfocyty MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory * MeSH
- podskupiny B-lymfocytů * MeSH
- receptory antigenů B-buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Despite the growing number of immune repertoire sequencing studies, the field still lacks software for analysis and comprehension of this high-dimensional data. Here we report VDJtools, a complementary software suite that solves a wide range of T cell receptor (TCR) repertoires post-analysis tasks, provides a detailed tabular output and publication-ready graphics, and is built on top of a flexible API. Using TCR datasets for a large cohort of unrelated healthy donors, twins, and multiple sclerosis patients we demonstrate that VDJtools greatly facilitates the analysis and leads to sound biological conclusions. VDJtools software and documentation are available at https://github.com/mikessh/vdjtools.
- MeSH
- dítě MeSH
- dospělí MeSH
- dvojčata genetika MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- receptory antigenů T-buněk chemie genetika metabolismus MeSH
- roztroušená skleróza genetika MeSH
- sekvenční analýza DNA metody MeSH
- shluková analýza MeSH
- software * MeSH
- transplantace hematopoetických kmenových buněk MeSH
- výpočetní biologie metody MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH