Cancer Institute A national cancer institute
designated cancer center

CD107a-Based Analysis of Tumor-Cytolytic T Cells

 PETER LEE, MD

During the process of cell killing, vesicles in effector CD8+ T cells fuse with the target cell membrane, releasing cytotoxic mediators such as perforin and granzymes. CD107a (also known as lysosomal-associated membrane protein-1) is a vesicle membrane protein that becomes transiently mobilized to the cell surface during this degranulation process.

The use of CD107a mobilization in flow cytometric analysis is now being used as a marker of degranulation. Peter Lee recently used CD107a mobilization to identify and isolate functional tumor-reactive T cells with high recognition efficiency directly from peripheral blood mononuclear cells of cancer patients after vaccination.

Dr. Lee showed that tumor-cytolytic T cells are indeed elicited in patients after cancer vaccination, and that tumor reactivity is strongly correlated with efficient T cell recognition of peptide-bearing targets. He combined CD107a mobilization with peptide-MHC tetramer staining to directly correlate antigen specificity and cytolytic ability on a single-cell level. This showed that tumor-cytolytic T cells with high recognition efficiency represent only a minority of peptide-specific T cells elicited in patients after heteroclitic peptide vaccination.

His group was also able to expand these cells to high numbers ex vivo while maintaining their cytolytic potential. These techniques, in addition to those described above, should prove useful not only for immune monitoring of cancer vaccine trials, but also for adoptive cellular immunotherapy after ex vivo expansion. The ability to rapidly identify and isolate tumor-cytolytic T cells should be useful in cancer immunotherapy.

 

Stanford Medicine Resources:

Footer Links: