Shailender Bhatia.

Julie R. Brahmer, M.D http://zithroma.com/reviews.html ., Scott S. Tykodi, M.D., Ph.D., Laura Q.M. Chow, M.D., Wen-Jen Hwu, M.D., Ph.D., Suzanne L. Topalian, M.D., Patrick Hwu, M.D., Charles G. Drake, M.D., Ph.D., Luis H. Camacho, M.D., M.P.H., John Kauh, M.D., Kunle Odunsi, M.D., Ph.D., Henry C. Pitot, M.D., Omid Hamid, M.D., Shailender Bhatia, M.D., Renato Martins, M.D., M.P.H., Keith Eaton, M.D., Ph.D., Shuming Chen, Ph.D., Theresa M. Salay, M.S., Suresh Alaparthy, Ph.D., Joseph F. Grosso, Ph.D., Alan J. Korman, Ph.D., Susan M. Parker, Ph.D., Shruti Agrawal, Ph.D., Stacie M. Goldberg, M.D., Drew M. Pardoll, M.D., Ph.D., Ashok Gupta, M.D., Ph.D., and Jon M. Wigginton, M.D.1 However, T-cell directed immunotherapy has been less successful.2 Despite the large number of tumor antigens induced by genetic and epigenetic changes within all cancers, tumors resist immune attack by inducing tolerance among tumor-particular T cells and by expressing ligands that engage inhibitory receptors and dampen T-cell functions within the tumor microenvironment.3 Preclinical and scientific data show that antibody blockade of these immune checkpoints may significantly enhance antitumor immunity.9 Programmed death 1 protein is definitely another T-cellular coinhibitory receptor with a structure identical to that of CTLA-4 but with a definite biologic function and ligand specificity.10,11 PD-1 provides two known ligands, PD-L1 12,13 and PD-L2 .14,15 In contrast to CTLA-4 ligands, CD80 and CD86 , PD-L1 is selectively expressed on many tumors16-18 and on cells within the tumor microenvironment in response to inflammatory stimuli.19 Blockade of the interaction between PD-1 and PD-L1 potentiates immune responses in vitro20 and mediates preclinical antitumor activity.16,17 PD-L1 is the primary PD-1 ligand that is up-regulated in great tumors, where it could inhibit cytokine production and the cytolytic activity of PD-1+, tumor-infiltrating CD8+ and CD4+ T cells.16,21,22 These properties help to make PD-L1 a potentially promising target for cancers immunotherapy.org.