Immunotherapy: It Takes a Village

摘要

We in the cancer immunology and immunotherapy community are thrilled that Science named "Cancer immunotherapy" as 2013's Breakthrough of the Year (J. Couzin-Frankel, 20 December 2013, p. 1432). The rapid succession of clinical successes by block- ing antibodies to two immune checkpoints, CTLA-4 and PD-1, and by chimeric antigen-receptor-transduced T cells, shows the power of basic immunology when translated to therapy. As such, I write to acknowledge some of the key scientists whose basic discoveries paved the way for the clinical successes outlined in the Breakthrough issue. CTLA-4 was originally cloned by Pierre Goldstein. Peter Linsley later demonstrated that its ligands were B7.1 and B7.2, in fact the same as for the T cell costimulatory receptor CD28. On the basis of in vitro studies, Jeffrey Bluestone first suggested that, in contrast to CD28, CTLA-4 was an inhibitory receptor. A year later, concurrent with similar in vitro findings from Jim Allison, Arlene Sharpe and Tak Mak independently proved CTLA-4's inhibitory function in genetic knockout mice. These discoveries paved the way for Allison's seminal work demonstrating in murine tumor models that CTLA-4 blockade induced antitumor responses, supporting its subsequent clinical development.