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Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery.

Publication ,  Journal Article
Campa, MJ; Moody, MA; Zhang, R; Liao, H-X; Gottlin, EB; Patz, EF
Published in: Cancer Immunol Immunother
February 2016

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.

Duke Scholars

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Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

February 2016

Volume

65

Issue

2

Start / End Page

171 / 180

Location

Germany

Related Subject Headings

  • Sequence Analysis, DNA
  • Sequence Alignment
  • Neoplasm Staging
  • Molecular Targeted Therapy
  • Molecular Sequence Data
  • Middle Aged
  • Male
  • Lymphocytes, Tumor-Infiltrating
  • Lung Neoplasms
  • Immunology
 

Citation

APA
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ICMJE
MLA
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Campa, M. J., Moody, M. A., Zhang, R., Liao, H.-X., Gottlin, E. B., & Patz, E. F. (2016). Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery. Cancer Immunol Immunother, 65(2), 171–180. https://doi.org/10.1007/s00262-015-1787-0
Campa, Michael J., M Anthony Moody, Ruijun Zhang, Hua-Xin Liao, Elizabeth B. Gottlin, and Edward F. Patz. “Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery.Cancer Immunol Immunother 65, no. 2 (February 2016): 171–80. https://doi.org/10.1007/s00262-015-1787-0.
Campa MJ, Moody MA, Zhang R, Liao H-X, Gottlin EB, Patz EF. Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery. Cancer Immunol Immunother. 2016 Feb;65(2):171–80.
Campa, Michael J., et al. “Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery.Cancer Immunol Immunother, vol. 65, no. 2, Feb. 2016, pp. 171–80. Pubmed, doi:10.1007/s00262-015-1787-0.
Campa MJ, Moody MA, Zhang R, Liao H-X, Gottlin EB, Patz EF. Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery. Cancer Immunol Immunother. 2016 Feb;65(2):171–180.
Journal cover image

Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

February 2016

Volume

65

Issue

2

Start / End Page

171 / 180

Location

Germany

Related Subject Headings

  • Sequence Analysis, DNA
  • Sequence Alignment
  • Neoplasm Staging
  • Molecular Targeted Therapy
  • Molecular Sequence Data
  • Middle Aged
  • Male
  • Lymphocytes, Tumor-Infiltrating
  • Lung Neoplasms
  • Immunology