Breaking through the central tolerance ceiling to unleash anticancer immune responses.

Central thymic tolerance mechanisms create a formidable barrier against the generation of self-reactive T cells. While preventing autoimmunity, this barrier also limits an effective antitumor immunological response. We recently reported that anti-RANKL blocking antibody breaches this central tolerance barrier, thus increasing the repertoire of melanoma reactive T cells. Thus, central tolerance blockade may be an effective therapeutic strategy to enhance anticancer immunity.