Nicholas P. Restifo

Nicholas P. Restifo (born July 24, 1960) is an American immunologist, physician and educator in cancer immunotherapy. He is a tenured senior investigator in the intramural National Cancer Institute of the National Institutes of Health at Bethesda, Maryland.^[1]

Dr. Restifo has been a pioneer in the use of T cell-based immunotherapy.

Early life and education

Dr. Restifo was born in Columbus, Ohio. He grew up in a small town, Amherst, Ohio, and went to high school in Lorain, Ohio. He completed his undergraduate education with honors at the Johns Hopkins University and obtained his medical degree from New York University School of Medicine. He first joined the National Cancer Institute, NIH in Bethesda, Maryland in 1989. He was recruited from the Memorial Sloan Kettering Cancer Center, where he worked in the laboratory of Murray Brennan, the former chairman of Surgery. He became a principal investigator ^[2] in 1993 and has authored or co-authored more than 300 papers and book chapters on cancer immunotherapy.^[3]

Research

Dr. Restifo's most recent efforts include a focus on how elements – literally from the periodic table – influence cancer immunity. These include work on how oxygen can inhibit anti-tumor immunity ^[4] and how potassium ions from dying cancer cells can shut down the anti-tumor response.^[5]

Successful treatment of patients with cancer is the goal of his laboratory, and his therapeutic approaches employ adoptive T cell transfer, gene modification and cellular reprogramming.^[6] Basic aspects of tumor and T cell immunology inform novel therapeutic interventions in the clinic.

Restifo and his research team have made contributions to the fields of adoptive cell transfer^[7]tumor immune-escape,^[8][9] virally encoded cancer vaccines,^[10] adoptive cell transfer for the treatment of cancer, and the biology of self/tumor-reactive T cells, with an emphasis on memory CD8+ T cells.^[11]

He identified a new class of intrinsic checkpoint inhibitors. They found that CISH, a member of the SOCS family of molecules to be induced by T cell receptor ligation (TCR) and negatively regulate it by targeting the critical signaling intermediate PLCG1 for degradation.^[12] The deletion of Cish in effector T cells has been shown to dramatically augment TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant increase in functional avidity and long-term tumor immunity. Surprisingly there was no changes in activity of Cish's purported target, STAT5. Thus Cish represents a new class of T-cell intrinsic immunologic checkpoints with the potential to radically enhance adoptive immunotherapies for cancer.

See also

• Cytotoxic T cell
• interleukin 15
• memory t cell
• Cish

References