Control of syngeneic tumor growth by activation of CD8(+) T cells: Efficacy is limited by migration away from the site and induction of nonresponsiveness

Activation of Ag-specific CD8(+) T cells in response to syngeneic tumor has been visualized by adoptive transfer of CD8(+) T cells from OT-I mice, wit h a transgenic TCR specific for H-2K(b) and an OVA peptide, into Thy-1 cong enic recipients, Intraperitoneal challenge with E.G7, the EL-4 thymoma tran sfected with OVA, results in activation and clonal expansion of the OT-I ce lls in the peritoneal cavity and transient control of turner growth, Howeve r, within 2 days after becoming activated, the OT-I cells migrate out of th e peritoneal cavity into the spleen and lymph nodes, and tumor growth resum es in the peritoneal cavity, The OT-I cells in lymph nodes and spleen have lytic effector activity, but exhibit split anergy in that they cannot proli ferate in response to Ag unless exogenous IL-2 is provided, The failure to remain at the tumor site and continue to control tumor growth is not due to selection of Ag loss variants or development of suppression. These results suggest that effective CD8-targeted immunotherapy may depend less on enhan cing the initial activation and more on sustaining the response at the appr opriate location and/or reactivating cells that have left the site of tumor growth and become nonresponsive.