Deep sequencing of the T cell receptor visualizes reconstitution of T cell immunity in mogamulizumab-treated adult T cell leukemia. (4th March 2018)

• Record Type: Journal Article
• Authors: Shindo, Takero; Kitaura, Kazutaka; Ureshino, Hiroshi; Kamachi, Kazuharu; Miyahara, Masaharu; Doi, Kazuko; Watanabe, Tatsuro; Sueoka, Eisaburo; Shin-I, Tadasu; Suzuki, Ryuji; Kimura, Shinya
• Is Part Of: Oncoimmunology. Volume 7:Number 3(2018)
• Publication Date: 2018-03-04
• Subjects: adult T cell leukemia -- mogamulizumab -- T cell receptor -- immune reconstitution -- next generation sequencing; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1405204
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4 + regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients. Treatment with moga resulted in remarkable reduction or elimination of clonal cells, and enhanced reconstitution of non-tumor polyclonal CD4 + T cells and oligoclonal CD8 + T cells. Interestingly, cutaneous T cells infiltrating moga-related skin rashes did not share the same major clones in peripheral blood, which minimizes the possibility of cross-reaction. Thus, deep sequencing of the TCR can reveal the immune reconstitution of moga-treated ATL and provides powerful insights into its mode of action.