CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth

Claus, Christina; Riether, Carsten; Schürch, Christian; Matter, Matthias S; Hilmenyuk, Tamara; Ochsenbein, Adrian (2012). CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth. Cancer research, 72(14), pp. 3664-76. Birmingham, Ala.: American Association for Cancer Research AACR 10.1158/0008-5472.CAN-11-2791

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Signaling of the TNF receptor superfamily member CD27 activates costimulatory pathways to elicit T- and B-cell responses. CD27 signaling is regulated by the expression of its ligand CD70 on subsets of dendritic cells and lymphocytes. Here, we analyzed the role of the CD27-CD70 interaction in the immunologic control of solid tumors in Cd27-deficient mice. In tumor-bearing wild-type mice, the CD27-CD70 interaction increased the frequency of regulatory T cells (Tregs), reduced tumor-specific T-cell responses, increased angiogenesis, and promoted tumor growth. CD27 signaling reduced apoptosis of Tregs in vivo and induced CD4(+) effector T cells (Teffs) to produce interleukin-2, a key survival factor for Tregs. Consequently, the frequency of Tregs and growth of solid tumors were reduced in Cd27-deficient mice or in wild-type mice treated with monoclonal antibody to block CD27 signaling. Our findings, therefore, provide a novel mechanism by which the adaptive immune system enhances tumor growth and may offer an attractive strategy to treat solid tumors.

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