Resolving intratumoral B cells and IG-producing plasma cell content is critical for our understanding of tumor-immunity interaction and its evolution, pro- and anti-cancer roles of distinct B cell subsets and specificities, fundamentals of response or resistance to immunotherapies.

Studies on the highly diverse B cells landscapes in tumor tissues can provide detailed insights on the tumor-immunity interactions, but require comprehensive in-depth analysis both at the bulk, tissue, and single-cell level, combining large-scale approaches with identification of antigen-specific B cells, linkage of transcriptomics and proteomics signatures with functional B cell programs, investigation of the spatial organization of B cell infiltrated zones and B cell interaction with T cells, other immune cells, and tumor.

Making sense of the tangled picture is challenging, and requires a whole arsenal of methods and approaches to unravel the phenotypic, functional, spatial, and antigen-specific landscape of B cells in the TME.

Such integral analysis becomes realistic with the current progress in single cell transcriptomics1, 2, 3, multicolor imaging4, 5, spatial transcriptomics6, 7, 8, approaches to identification of B cell specificity9, 10, 11, 12, 13, 14 along with the developing wet lab and bioinformatics tools to investigate the architecture of BCR repertoires and clonal lineages of hypermutating BCR variants (Fig. 1).

Here we attempt to cover and structure the diversity of these rapidly evolving tools.