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Patients who have anti-SOX2 T cells (solid line) are less likely to develop multiple myeloma than those lacking these T cells (dashed line).
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The immune system can only prevent cancer if it recognizes and destroys precancerous cells. Antigenic targets of such an early immune response, however, have been elusive. Spisek et al. (page 831) now find that an embryonic stem cell marker is a bull's eye for immune cells in patients who have precancerous lesions but never develop multiple myeloma.
Multiple myeloma is an incurable cancer that occurs throughout the bone marrow. It is caused by the uncontrolled proliferation of antibody-producing B cells, which replace normal immune cells as well as red blood cells and platelets. In some patients, this malignant cancer is preceded by a benign condition known as multiple gammopathy of undetermined significance (MGUS). During this stage, the abnormal B cells do not form tumors, and the patients remain healthy. Although MGUS occurs in 
3% of the population over 50 years of age, only a third of those with MGUS will eventually develop myeloma.
This selective disease protection, the team now shows, correlates with the presence of immune responses against the embryonic transcription factor SOX2. SOX2 is normally switched off after embryonic stem cells differentiate, but, in both MGUS and myeloma patients, it is reactivated in bone marrow cells that are potential tumor progenitors. MGUS patients had anti-SOX2 antibodies and T cells, but the myeloma patients did not. In a two-year observational study, patients with early tumors who had anti-SOX2 T cells remained cancer-free. Those that lacked these T cells, however, developed multiple myeloma.
These findings suggest that an immune response against the SOX2-expressing bone marrow cells may prevent malignancy. The group is now trying to determine whether myeloma patients never mount an immune response to SOX2 or simply lose it over time. The group's in vitro evidence suggests that anti-SOX2 T cells prevent tumor formation. But myeloma patients would have to be vaccinated against SOX2 to confirm that these T cells have antitumor activity in vivo. 
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