The authors show that when cancer develops in mouse skin cells, Tregs accumulate in tumors, yet CD8+ Teff cells are underrepresented. They go on to demonstrate that blockade of CTLA4 lifts the inhibition of T cell proliferation and allows both Tregs and Teff cells to proliferate in response to exposure to self-antigen. Interestingly, combination of CLTA4 blockade with Gvax selectively primes the anti-tumor Teff cells for action. This led to greater infiltration of Teff cells into the tumor, and eventually to tumor rejection. Importantly, the authors report that chronic exposure to anti- CLTA4 or to the Gvax/anti-CTLA4 combination therapy does not deplete the number of Tregs, nor their regulatory activity, which suggests that upon completion of this therapy these cells would still be able to control possible adverse immune responses.
Journal of Clinical Investigation