title: Covert operations: cancer's many subversive tactics in overcoming host defenses.
abstract: 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.
authors.affiliation: dlongo@nejm.org
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D056724:Immunity, Humoral / Q000502:physiology*; D056747:Immunomodulation; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D013601:T-Lymphocytes