Deep sequencing of the T cell receptor visualizes reconstitution of T cell immunity in mogamulizumab-treated adult T cell leukemia

• Main Authors: Takero Shindo, Kazutaka Kitaura, Hiroshi Ureshino, Kazuharu Kamachi, Masaharu Miyahara, Kazuko Doi, Tatsuro Watanabe, Eisaburo Sueoka, Tadasu Shin-I, Ryuji Suzuki, Shinya Kimura
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2018-03-01
• Series: OncoImmunology
• Subjects: adult t cell leukemia; mogamulizumab; t cell receptor; immune reconstitution; next generation sequencing
• Online Access: http://dx.doi.org/10.1080/2162402X.2017.1405204

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.