ATM activity in T cells is critical for immune surveillance of lymphoma in vivo

Arina Riabinska*, Daria Lehrmann, Ron Daniel Jachimowicz, Gero Knittel, Christian Fritz, Anna Schmitt, Aenne Geyer, Carola Heneweer, Maike Wittersheim, Lukas P. Frenzel, Alessandro Torgovnick, Janica Lea Wiederstein, Claudia Maria Wunderlich, Monika Ortmann, Arlette Paillard, Wilhelm Wößmann, Arndt Borkhardt, Stefan Burdach, Martin Leo Hansmann, Andreas RosenwaldSven Perner, Gita Mall, Wolfram Klapper, Andrea Merseburg, Marcus Krüger, Holger Grüll, Thorsten Persigehl, Frank Thomas Wunderlich, Martin Peifer, Olaf Utermöhlen, Reinhard Büttner, Filippo Beleggia, Hans Christian Reinhardt

*Corresponding author for this work
2 Citations (Scopus)


The proximal DNA damage response kinase ATM is frequently inactivated in human malignancies. Germline mutations in the ATM gene cause Ataxia-telangiectasia (A-T), characterized by cerebellar ataxia and cancer predisposition. Whether ATM deficiency impacts on tumor initiation or also on the maintenance of the malignant state is unclear. Here, we show that Atm reactivation in initially Atm-deficient B- and T cell lymphomas induces tumor regression. We further find a reduced T cell abundance in B cell lymphomas from Atm-defective mice and A-T patients. Using T cell-specific Atm-knockout models, as well as allogeneic transplantation experiments, we pinpoint impaired immune surveillance as a contributor to cancer predisposition and development. Moreover, we demonstrate that Atm-deficient T cells display impaired proliferation capacity upon stimulation, due to replication stress. Altogether, our data indicate that T cell-specific restoration of ATM activity or allogeneic hematopoietic stem cell transplantation may prevent lymphomagenesis in A-T patients.

Original languageEnglish
Issue number3
Pages (from-to)771-786
Number of pages16
Publication statusPublished - 01.03.2020


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