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      Tumor-infiltrating B cells : The ignored players in tumor immunology

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          Abstract

          B cells infiltrating into solid tumors are poorly investigated despite their described positive prognostic value. Whether this antitumor potential comes from either the antigen presentation or the antibody production capacity of B cells, or both, is unknown. Our recently published method on tumor-infiltrating B lymphocyte cloning may prove helpful in unraveling the actual relevance of these cells for tumor development and response to therapy.

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          Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma.

          Gulsun Erdag, Jochen Schaefer, Mark Smolkin … (2012)
          Immune cells infiltrating the microenvironment of melanoma metastases may either limit or promote tumor progression, but the characteristics that distinguish these effects are obscure. In this study, we systematically evaluated the composition and organization of immune cells that infiltrated melanoma metastases in human patients. Three histologic patterns of immune cell infiltration were identified, designated immunotypes A, B, and C. Immunotype A was characterized by no immune cell infiltrate. Immunotype B was characterized by infiltration of immune cells limited only to regions proximal to intratumoral blood vessels. Immunotype C was characterized by a diffuse immune cell infiltrate throughout a metastatic tumor. These immunotypes represented 29%, 63%, and 8% of metastases with estimated median survival periods of 15, 23, and 130 months, respectively. Notably, from immunotypes A to C, there were increasing proportions of B cells and decreasing proportions of macrophages. Overall, the predominant immune cells were T cells (53%), B cell lineage cells (33%), and macrophages (13%), with natural killer and mature dendritic cells only rarely present. Whereas higher densities of CD8(+) T cells correlated best with survival, a higher density of CD45(+) leukocytes, T cells, and B cells also correlated with increased survival. Together, our findings reveal striking differences in the immune infiltrate in melanoma metastases in patients, suggesting microenvironmental differences in immune homing receptors and ligands that affect immune cell recruitment. These findings are important, not only by revealing how the immune microenvironment can affect outcomes but also because they reveal characteristics that may help improve individualized therapy for patients with metastatic melanoma.
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            Systematic Analysis of Immune Infiltrates in High-Grade Serous Ovarian Cancer Reveals CD20, FoxP3 and TIA-1 as Positive Prognostic Factors

            Katy Milne, Martin Köbel, Steven Kalloger … (2009)
            Background Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC), but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC. Methodology/Principal Findings Tissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases) and myeloperoxidase (negative association in clear cell cases). Conclusions/Significance Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.
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              Naturally occurring B-cell responses to breast cancer.

              Tammara A. Wood, E Hersh (2003)
              As demonstrated by the effectiveness of trastuzumab, antibodies against breast cancer antigens are a potentially potent mechanism of tumor control. While trastuzumab is administered exogenously, its efficacy suggests that induction of very high titer antibody responses in vivo might also be therapeutic. Both naturally occurring and vaccine-induced antibody responses to some breast cancer antigens are associated with improved survival in some cases. However, the improvement in survival associated with antibody responses to breast cancer is modest, and tumor regression is not known to be associated with the natural antitumor antibody response, indicating a need for improved understanding of the natural antitumor antibody response. Naturally occurring B-cell responses in the form of serum antibody, tumor reactive lymph node B cells, and tumor-infiltrating B cells have been described, and a variety of breast tumor-associated antigens have been identified based on reactivity of patient antibodies. This review discusses current knowledge of humoral immunity to breast cancer with regard to specific antigens and the basis for their immunogenicity, and the contexts (tumor, lymph node, serum) in which responses are observed. With few exceptions, "tumor-associated antigens" identified with naturally occurring antibodies may be overexpressed on tumor but are in fact nonspecific autoantigens. This suggests that while overexpression or aberrant processing can increase immunogenicity in some cases, the immunogenicity of many or even most tumor-associated antigens is a function of expression in tumor or the result of ancillary tumor factors.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncoimmunology
                Journal ID (iso-abbrev): Oncoimmunology
                Journal ID (publisher-id): ONCI
                Title: Oncoimmunology
                Publisher: Landes Bioscience
                ISSN (Print): 2162-4011
                ISSN (Electronic): 2162-402X
                Publication date (Print): 01 October 2012
                Publication date PMC-release: 01 October 2012
                Volume: 1
                Issue: 7
                Pages: 1186-1188
                Affiliations
                Division of Molecular Oncology and Immunotherapy; Department of General Surgery; University of Rostock; Rostock, Germany
                Author notes
                [* ]Correspondence to: Michael Linnebacher, Email: Michael.linnebacher@ 123456med.uni-rostock.de
                Article
                Publisher ID: 2012ONCOIMM0153 Publisher Item ID: 20641
                DOI: 10.4161/onci.20641
                PMC ID: 3494640
                PubMed ID: 23170274
                SO-VID: c3f2ae3b-d62a-4720-bc8d-1f4cc2ae199c
                Copyright © Copyright © 2012 Landes Bioscience
                License:

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

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                Subject: Author's View

                ScienceOpen disciplines: Immunology
                Keywords: tumor-infiltrating lymphocytes,tumor host interaction,tumor immunology,tumor-infiltrating b cells,b cell subtypes
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                ScienceOpen disciplines: Immunology
                Keywords: tumor-infiltrating lymphocytes, tumor host interaction, tumor immunology, tumor-infiltrating b cells, b cell subtypes

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