Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases

Lymphoid neogenesis, or the development of lymphoid structures in nonlymphoid organs, is frequently observed in chronically inflamed tissues, during the course of autoimmune, infectious, and chronic graft rejection diseases, in which a sustained lymphocyte activation occurs in the presence of persis...

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Vydáno v:	Cancer research (Chicago, Ill.) Ročník 72; číslo 16; s. 3997
Hlavní autoři:	Cipponi, Arcadi, Mercier, Marjorie, Seremet, Teofila, Baurain, Jean-François, Théate, Ivan, van den Oord, Joost, Stas, Marguerite, Boon, Thierry, Coulie, Pierre G, van Baren, Nicolas
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 15.08.2012
Témata:	Antibodies, Neoplasm - biosynthesis Antibodies, Neoplasm - immunology B-Lymphocytes - immunology Case-Control Studies Genes, Immunoglobulin Germinal Center - immunology Germinal Center - pathology Humans Immunohistochemistry Lymphoid Tissue - immunology Lymphoid Tissue - pathology Melanoma - genetics Melanoma - immunology Melanoma - pathology Melanoma - secondary Skin Neoplasms - genetics Skin Neoplasms - immunology Skin Neoplasms - pathology Skin Neoplasms - secondary
ISSN:	1538-7445, 1538-7445
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Abstract	Lymphoid neogenesis, or the development of lymphoid structures in nonlymphoid organs, is frequently observed in chronically inflamed tissues, during the course of autoimmune, infectious, and chronic graft rejection diseases, in which a sustained lymphocyte activation occurs in the presence of persistent antigenic stimuli. The presence of such ectopic lymphoid structures has also been reported in primary lung, breast, and germline cancers, but not yet in melanoma. In this study, we observed ectopic lymphoid structures, defined as lymphoid follicles comprising clusters of B lymphocytes and follicular dendritic cells (DC), associated with high endothelial venules (HEV) and clusters of T cells and mature DCs, in 7 of 29 cutaneous metastases from melanoma patients. Some follicles contained germinal centers. In contrast to metastatic lesions, primary melanomas did not host follicles, but many contained HEVs, suggesting an incomplete lymphoid neogenesis. Analysis of the repertoire of rearranged immunoglobulin genes in the B cells of microdissected follicles revealed clonal amplification, somatic mutation and isotype switching, indicating a local antigen-driven B-cell response. Surprisingly, IgA responses were observed despite the nonmucosal location of the follicles. Taken together, our findings show the existence of lymphoid neogenesis in melanoma and suggest that the presence of functional ectopic lymphoid structures in direct contact with the tumor makes the local development of antimelanoma B- and T-cell responses possible.
AbstractList	Lymphoid neogenesis, or the development of lymphoid structures in nonlymphoid organs, is frequently observed in chronically inflamed tissues, during the course of autoimmune, infectious, and chronic graft rejection diseases, in which a sustained lymphocyte activation occurs in the presence of persistent antigenic stimuli. The presence of such ectopic lymphoid structures has also been reported in primary lung, breast, and germline cancers, but not yet in melanoma. In this study, we observed ectopic lymphoid structures, defined as lymphoid follicles comprising clusters of B lymphocytes and follicular dendritic cells (DC), associated with high endothelial venules (HEV) and clusters of T cells and mature DCs, in 7 of 29 cutaneous metastases from melanoma patients. Some follicles contained germinal centers. In contrast to metastatic lesions, primary melanomas did not host follicles, but many contained HEVs, suggesting an incomplete lymphoid neogenesis. Analysis of the repertoire of rearranged immunoglobulin genes in the B cells of microdissected follicles revealed clonal amplification, somatic mutation and isotype switching, indicating a local antigen-driven B-cell response. Surprisingly, IgA responses were observed despite the nonmucosal location of the follicles. Taken together, our findings show the existence of lymphoid neogenesis in melanoma and suggest that the presence of functional ectopic lymphoid structures in direct contact with the tumor makes the local development of antimelanoma B- and T-cell responses possible.Lymphoid neogenesis, or the development of lymphoid structures in nonlymphoid organs, is frequently observed in chronically inflamed tissues, during the course of autoimmune, infectious, and chronic graft rejection diseases, in which a sustained lymphocyte activation occurs in the presence of persistent antigenic stimuli. The presence of such ectopic lymphoid structures has also been reported in primary lung, breast, and germline cancers, but not yet in melanoma. In this study, we observed ectopic lymphoid structures, defined as lymphoid follicles comprising clusters of B lymphocytes and follicular dendritic cells (DC), associated with high endothelial venules (HEV) and clusters of T cells and mature DCs, in 7 of 29 cutaneous metastases from melanoma patients. Some follicles contained germinal centers. In contrast to metastatic lesions, primary melanomas did not host follicles, but many contained HEVs, suggesting an incomplete lymphoid neogenesis. Analysis of the repertoire of rearranged immunoglobulin genes in the B cells of microdissected follicles revealed clonal amplification, somatic mutation and isotype switching, indicating a local antigen-driven B-cell response. Surprisingly, IgA responses were observed despite the nonmucosal location of the follicles. Taken together, our findings show the existence of lymphoid neogenesis in melanoma and suggest that the presence of functional ectopic lymphoid structures in direct contact with the tumor makes the local development of antimelanoma B- and T-cell responses possible. Lymphoid neogenesis, or the development of lymphoid structures in nonlymphoid organs, is frequently observed in chronically inflamed tissues, during the course of autoimmune, infectious, and chronic graft rejection diseases, in which a sustained lymphocyte activation occurs in the presence of persistent antigenic stimuli. The presence of such ectopic lymphoid structures has also been reported in primary lung, breast, and germline cancers, but not yet in melanoma. In this study, we observed ectopic lymphoid structures, defined as lymphoid follicles comprising clusters of B lymphocytes and follicular dendritic cells (DC), associated with high endothelial venules (HEV) and clusters of T cells and mature DCs, in 7 of 29 cutaneous metastases from melanoma patients. Some follicles contained germinal centers. In contrast to metastatic lesions, primary melanomas did not host follicles, but many contained HEVs, suggesting an incomplete lymphoid neogenesis. Analysis of the repertoire of rearranged immunoglobulin genes in the B cells of microdissected follicles revealed clonal amplification, somatic mutation and isotype switching, indicating a local antigen-driven B-cell response. Surprisingly, IgA responses were observed despite the nonmucosal location of the follicles. Taken together, our findings show the existence of lymphoid neogenesis in melanoma and suggest that the presence of functional ectopic lymphoid structures in direct contact with the tumor makes the local development of antimelanoma B- and T-cell responses possible.
Author	Boon, Thierry Baurain, Jean-François van Baren, Nicolas Cipponi, Arcadi Coulie, Pierre G Théate, Ivan Seremet, Teofila van den Oord, Joost Stas, Marguerite Mercier, Marjorie
Author_xml	– sequence: 1 givenname: Arcadi surname: Cipponi fullname: Cipponi, Arcadi organization: de Duve Institute, Université catholique de Louvain, Bruxelles, Belgium – sequence: 2 givenname: Marjorie surname: Mercier fullname: Mercier, Marjorie – sequence: 3 givenname: Teofila surname: Seremet fullname: Seremet, Teofila – sequence: 4 givenname: Jean-François surname: Baurain fullname: Baurain, Jean-François – sequence: 5 givenname: Ivan surname: Théate fullname: Théate, Ivan – sequence: 6 givenname: Joost surname: van den Oord fullname: van den Oord, Joost – sequence: 7 givenname: Marguerite surname: Stas fullname: Stas, Marguerite – sequence: 8 givenname: Thierry surname: Boon fullname: Boon, Thierry – sequence: 9 givenname: Pierre G surname: Coulie fullname: Coulie, Pierre G – sequence: 10 givenname: Nicolas surname: van Baren fullname: van Baren, Nicolas
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/22850419$$D View this record in MEDLINE/PubMed
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SubjectTerms	Antibodies, Neoplasm - biosynthesis Antibodies, Neoplasm - immunology B-Lymphocytes - immunology Case-Control Studies Genes, Immunoglobulin Germinal Center - immunology Germinal Center - pathology Humans Immunohistochemistry Lymphoid Tissue - immunology Lymphoid Tissue - pathology Melanoma - genetics Melanoma - immunology Melanoma - pathology Melanoma - secondary Skin Neoplasms - genetics Skin Neoplasms - immunology Skin Neoplasms - pathology Skin Neoplasms - secondary
Title	Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases
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