ABSTRACT
There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size. Recombinant antibodies from clonal families bound non-autologous tumor tissue and cell lines, and families possessing immunoglobulin paratope sequence motifs shared across patients exhibited increased rates of binding. We identified antibodies that caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. Our findings demonstrate convergent functional anti-tumor antibody responses targeting public tumor antigens, and provide an approach to identify antibodies with diagnostic or therapeutic utility.
Subject(s)
Antigens, Neoplasm/immunology , B-Lymphocytes/immunology , Neoplasms/immunology , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/secondary , Adult , Aged , Aged, 80 and over , Antibodies , Binding Sites, Antibody/immunology , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/secondary , Disease Progression , Female , Humans , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Melanoma/immunology , Melanoma/secondary , Middle Aged , Neoplasm Metastasis , Plasma Cells/immunology , Precursor Cells, B-Lymphoid , Skin Neoplasms/immunology , Skin Neoplasms/pathologyABSTRACT
After the completion of the genomic sequence of Arabidopsis thaliana, it is now a priority to identify all the genes, their patterns of expression and functions. Transcript profiling is playing a substantial role in annotating and determining gene functions, having advanced from one-gene-at-a-time methods to technologies that provide a holistic view of the genome. In this review, comprehensive transcript profiling methodologies are described, including two that are used extensively by the authors, cDNA-AFLP and cDNA microarraying. Both these technologies illustrate the requirement to integrate molecular biology, automation, LIMS and data analysis. With so much uncharted territory in the Arabidopsis genome, and the desire to tackle complex biological traits, such integrated systems will provide a rich source of data for the correlative, functional annotation of genes.
