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J Immunol ; 198(9): 3719-3728, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28348270

RESUMO

The B cells inhabited in mucosa play a vital role in mediating homeostasis with autoantigens and external Ags. Tumor-infiltrating lymphocytes are potential prognostic markers and therapeutic agents for cancer. However, the spatial heterogeneity of the B cell repertoire in intestinal mucosa and the tumor-infiltrating lymphocytes in colorectal cancer (CRC) remain poorly understood. In this study, we developed an unbiased method to amplify the IgH repertoire, as well as a bioinformatic pipeline to process these high-throughput sequencing data. With biopsies from seven intestinal mucosal segments, we uncovered their strong spatial homogeneity among the large intestine, where the clone overlap rate was up to 62.21%. The heterogeneity between terminal ileum and large intestine was also observed, including discrepant isotype distribution and low clone overlap rate. With tumor and adjacent normal mucosal tissues from CRC and colorectal advanced adenoma (AD) patients, we observed a similar IgH profile between tumor and adjacent normal mucosal tissues in AD, as well as a slight difference in CRC. Interestingly, we found distinct repertoire properties in the CRC tumor from AD and normal mucosa. Finally, we identified 1445 public clones for the normal mucosa, and 22 public clones for the CRC tumor with characteristic features. These data may be of potential use in clinical prognosis, diagnosis, and treatment of CRC.


Assuntos
Adenoma/imunologia , Linfócitos B/fisiologia , Neoplasias do Colo/imunologia , Neoplasias Colorretais/imunologia , Mucosa Intestinal/imunologia , Linfócitos do Interstício Tumoral/fisiologia , Receptores de Antígenos de Linfócitos B/genética , Adenoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Biologia Computacional , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias
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