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* Department of Neurology, Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA 02115;
Department of Neurology, Harvard Medical School, Boston, MA 02115;
Department of Neurosurgery, The Neurological Institute, Columbia University College of Physicians and Surgeons. New York, NY 10032; and
Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
Germ cell tumors are a heterogeneous group of neoplasms derived from residual primordial tissue. These tumors are commonly found in the brain, testes, or ovaries, where they are termed germinomas, seminomas, or dysgerminomas, respectively. Like several other tumor types, germ cell tumors often harbor an immune cell infiltrate that can include substantial numbers of B cells. Yet little is known about whether the humoral immune response affects germ cell tumor biology. To gain a deeper understanding of the role B cells play in this tumor family, we characterized the immune cell infiltrate of all three germ cell tumor subtypes and defined the molecular characteristics of the B cell Ag receptor expressed by tumor-associated B cells. Immunohistochemistry revealed a prominent B cell infiltrate in the microenvironment of all tumors examined and clear evidence of extranodal lymphoid follicles with germinal center-like architecture in a subset of specimens. Molecular characterization of the Ig variable region from 320 sequences expressed by germ cell tumor-infiltrating B cells revealed clear evidence of Ag experience, in that the cardinal features of an Ag-driven B cell response were present: significant somatic mutation, isotype switching, and codon insertion/deletion. This characterization also revealed the presence of both B cell clonal expansion and variation, suggesting that local B cell maturation most likely occurs within the tumor microenvironment. In contrast, sequences from control tissues and peripheral blood displayed none of these characteristics. Collectively, these data strongly suggest that an adaptive and specific humoral immune response is occurring within the tumor microenvironment.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by a grant from the Pediatric Brain Tumor Society (to S.N.W. and K.C.O.). S.N.W. is supported by a C. J. Martin Postdoctoral Fellowship from the National Health and Medical Research Council of Australia. K.C.O. is a Career Transition Fellow of the National Multiple Sclerosis Society.
2 Address correspondence and reprint requests to Dr. Kevin C. O’Connor, Brigham and Women’s Hospital, Center for Neurologic Diseases, NRB 641, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115. E-mail address: koconnor{at}rics.bwh.harvard.edu
3 Abbreviations used in this paper: TIL, tumor-infiltrating cell; DAB, diaminobenzidine; LCM, laser capture microdissection; FDC, follicular dendritic cell.
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