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Oncoimmunology. 2018 Sep 6;7(12):e1504728. doi: 10.1080/2162402X.2018.1504728. eCollection 2018.

Somatic mutation-associated T follicular helper cell elevation in lung adenocarcinoma.

Author information

1
British Columbia Cancer Research Centre, Integrative Oncology Department, Vancouver, Canada.
2
Faculty of Medicine, University of British Columbia, Vancouver, Canada.
3
Deeley Research Centre, Victoria, Canada.
4
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
5
Department of Zoology, University of British Columbia, Vancouver, Canada.

Abstract

T follicular helper cells (Tfh) play crucial roles in the development of humoral immunity. In the B cell-rich germinal center of lymphoid organs, they select for high-affinity B cells and aid in their maturation. While Tfh have known roles in B cell malignancies and have prognostic value in some epithelial cancers, their role in lung tumour initiation and development is unknown. Through immune cell deconvolution, we observed significantly increased Tfh in tumours from two independent cohorts of lung adenocarcinomas and found that this upregulation occurs early in tumour development. A subset of tumours were stained for T and B cells using multicolour immunohistochemistry, which revealed the presence of tumour-adjacent tertiary lymphoid organs in 17/20 cases each with an average of 16 Tfh observed in the germinal center. Importantly, Tfh levels were correlated with tumour mutational load and immunogenic cancer testis antigens, suggesting their involvement in mounting an active immune response against tumour neoantigens.

KEYWORDS:

CT antigen; T follicular helper cell; lung adenocarcinoma; neoantigen; tertiary lymphoid organ

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