Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery.
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Intratumoral B lymphocytes are an integral part of the lung tumor microenvironment. Interrogation of the antibodies they express may improve our understanding of the host response to cancer and could be useful in elucidating novel molecular targets. We used two strategies to explore the repertoire of intratumoral B cell antibodies. First, we cloned VH and VL genes from single intratumoral B lymphocytes isolated from one lung tumor, expressed the genes as recombinant mAbs, and used the mAbs to identify the cognate tumor antigens. The Igs derived from intratumoral B cells demonstrated class switching, with a mean VH mutation frequency of 4%. Although there was no evidence for clonal expansion, these data are consistent with antigen-driven somatic hypermutation. Individual recombinant antibodies were polyreactive, although one clone demonstrated preferential immunoreactivity with tropomyosin 4 (TPM4). We found that higher levels of TPM4 antibodies were more common in cancer patients, but measurement of TPM4 antibody levels was not a sensitive test for detecting cancer. Second, in an effort to focus our recombinant antibody expression efforts on those B cells that displayed evidence of clonal expansion driven by antigen stimulation, we performed deep sequencing of the Ig genes of B cells collected from seven different tumors. Deep sequencing demonstrated somatic hypermutation but no dominant clones. These strategies may be useful for the study of B cell antibody expression, although identification of a dominant clone and unique therapeutic targets may require extensive investigation.
SubjectIntratumoral B lymphocytes
Non-small cell lung cancer
Amino Acid Sequence
Molecular Sequence Data
Molecular Targeted Therapy
Sequence Analysis, DNA
Published Version (Please cite this version)10.1007/s00262-015-1787-0
Publication InfoCampa, Michael Joseph; Gottlin, EB; Liao, Hua-Xin; Moody, M Anthony; Patz, EF; & Zhang, R (2016). Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery. Cancer Immunol Immunother, 65(2). pp. 171-180. 10.1007/s00262-015-1787-0. Retrieved from http://hdl.handle.net/10161/11569.
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Associate Professor in Radiology
There is longstanding evidence that invasive lung cancer is the end result of a multi-step process in which progressive molecular changes herald and accompany cytomorphologic changes. Our knowledge of these molecular events and the specific markers associated with the evolution from initiation to invasion is only partial. A number of specific biomarkers involved in oncogene activation or inactivation of tumor suppressor genes have been identified, but no single marker to date has been show
Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute. Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus) from Apodemus agraius using tissue culture in China. The successful identification and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease, and advancement of HFRS research towards prevention by de
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