Anti-CTLA-4 immunotherapy does not deplete FOXP3+ regulatory T cells (Tregs) in human cancers-Letter

The potential role of anti-CTLA-4 antibodies in depleting intratumoral T-regulatory cells (iTregs) is still a matter of debate. In fact, if on one hand a recent study showed that ipilimumab and tremelimumab do not reduce Tregs in bladder, prostate and melanoma human cancers, on the other hand several other reports described opposite results. Basically, the depletion of iTregs may concern only CTLA-4+ iTregs and the evaluation of this population by immunohistochemistry may be challenging because CTLA-4 is highly express in the cytoplasm rather than on the membrane of these cells. In addition, the depletion of iTregs may occur selectively in patients with response to CTLA-4 inhibitors, a minority of the population treated with these drugs. The depletion of iTregs appears as a rapid phenomenon both in humans and mice, therefore biopsies should be performed early after the initiation of anti-CTLA-4 agents. Finally, the characterization of FCR repertoire and of the intratumoral innate immune cells able to perform antibody-derived cell-cytotoxicity should be reported to better evaluate the Tregs depleting properties of CTLA-4 inhibitors.

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