Covert operations: cancer's many subversive tactics in overcoming host defenses

In an effort to use the patient's T cells to fight his or her own cancer, we inadvertently discovered a distinctive form of tumor-induced immune suppression. T cells from tumor-bearing patients are often defective in signaling. They lack the zeta chain of the T-cell receptor and the src kinases crucial for its downstream effects including lck. They truncate the carboxy terminal of the p50 NF-kappaB transcription factor. At the population level, CD4 T cells are polarized toward the Th2 subtype and inhibitory Tregs expand. These T cells can recover after several days of culture outside of the tumor-bearing host environment. The effect is mediated by one or more factors made by the tumor given that the same T-cell defects occur in mice with tumors implanted in hollow fibers that never directly contact cells of the host. Several promising strategies may overcome these immunosuppressive effects.