Targeting Immunosupportive Cancer Therapies: Accentuate the Positive, Eliminate the Negative  Karl S. Peggs, Neil H. Segal, James P. Allison  Cancer Cell  Volume 12, Issue 3, Pages 192-199 (September 2007) DOI: 10.1016/j.ccr.2007.08.023 Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 1 The Genomic Instability of Cancers Is Important Both in the Evolution of Their Malignant Phenotype and in Providing Potential Targets for Immune-Based Therapeutics Mutant gene products, such as BCR-ABL or constitutively active epidermal growth factor receptor, provide potential targets for small-molecule inhibitors (SMIs) or monoclonal antibodies (mAbs). These, or other cytotoxic therapies, can indirectly enhance presentation of neoantigens via both the class II and class I MHC pathways of professional antigen-presenting cells. However, numerous regulatory circuits serve to limit the potential immune response directed toward these targets. Blockade of T cell-autonomous inhibitory pathways (e.g., CTLA-4) or inhibitory cellular populations (e.g., Foxp3+ regulatory T cells) may sufficiently enhance endogenous immune responses to enable the unmasking of clinically meaningful antitumor activity. B7x and B7H3 are newer inhibitory members of the CD28:B7 immunoglobulin superfamily that may also be amenable to blockade. Cancer Cell 2007 12, 192-199DOI: (10.1016/j.ccr.2007.08.023) Copyright © 2007 Elsevier Inc. Terms and Conditions