Purpose:A precise understanding of the mechanisms by which human immune cell subsets affect tumor biology will be critical for successful treatment of cancer using immunotherapeutic approaches. Recent evidence suggests that B cells can both promote and inhibit the development and progression of tumors. The aim of this study was to characterize the composition of the B-cell infiltrates in colorectal cancers (CRC) in order to gain further insight into the role of B cells in CRC.Experimental Design:In this study we characterized B-cell subsets in primary tumors (n=38), metastases (n=6) and blood (n=46) of 51 patients with a diagnosis of CRC and blood of 10 healthy controls. B-cell subsets were analyzed by flow cytometry or immunohistochemistry.Results:Peripheral blood of CRC patients contained a higher percentage of memory B cells than that of age-matched healthy controls. Furthermore, the percentage of B cells within tumors was higher than that in the peripheral blood of CRC patients while metastases were typically devoid of tumor-infiltrating B cells. Tumor-associated B cells were enriched for activated and terminally differentiated B cells. Relevant proportions of regulatory B cells could only be detected in advanced cancer and metastases.Conclusion:B cells constitute a significant proportion of the immune infiltrate in CRC. The B-cell infiltrate of primary CRC is characterized by an accumulation of terminally differentiated memory B cells or plasma cells suggestive of a specific immune response against the tumor. However advanced tumors and metastases are also infiltrated by a considerable number of regulatory B cells.

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The ex vivo expansion of human hematopoietic stem/progenitor cells (HSPCs) has important applications in both basic research and clinical transplantation therapy. Here, we introduce the protocol of a novel culture system that supports the long-term ex vivo expansion of human HSPCs, achieved through the complete replacement of cytokines and albumin by chemical agonists and a caprolactambased polymer. A phosphoinositide 3-kinase activator in combination with a thrombopoietin receptor agonist and the pyrimidoindole derivative UM171 were su cient to stimulate functional expansion of umbilical cord blood-derived HSCs. We envision that this chemically de ned expansion culture system will help to advance clinical HSC therapies.