Description

Immunoediting caused by TCR engagement reverses checkpoint between NK and nascent T cell lymphoma cells

Jürgen R. Müller, Lionel Feigenbaum, Thomas A. Waldmann and Sigrid Dubois

National Institutes of Health, National Cancer Institute, Lymphoid Malignancies Branch

Immunoediting describes a tumor-induced alteration of itself or of the immune surveillance system allowing tumor escape. Here we describe an inducible editing step during murine T cell lymphomagenesis. A high incidence of T cell lymphomas is known to occur in TCR-transgenic mice. We observed that NK cells established a checkpoint in initial stages that caused the elimination of nascent lymphoma cells, therefore allowing high lymphoma incidence in NK cell-depleted TCR-transgenic mice. T cell lymphomas were characterized by a distinct surface phenotype, and half had acquired Notch1 mutations. The elimination phase was concluded once nascent lymphoma cells encountered their antigen: A TCR engagement induced the production of a soluble NK cell toxin by the lymphoma cells allowing tumor growth in immunocompetent hosts. These data describe an immunoediting mechanism that causes the elimination of surveilling cells. It may also suggest the involvement of TCR engagement in the development of some T cell lymphomas.