Releasing the Brakes on Cancer Immunotherapy

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Releasing the Brakes on Cancer Immunotherapy Dan R. Littman Cell Volume 162, Issue 6, Pages 1186-1190 (September 2015) DOI: 10.1016/j.cell.2015.08.038 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Activation of Anti-Tumor Cytotoxic T Cells by Blockade of CTLA-4 Proposed mechanisms for the activity of anti-CTLA-4 antibody in releasing inhibition of tumor cell killing by CD8+ T cells. (Pathway 1) Indirect mechanism through inhibition of regulatory T cell (Treg) accumulation in tumors, which requires binding of antibody to Fc receptor on innate immune cells and is mediated by antibody-dependent cellular cytotoxicity. (Pathway 2) Direct activity on cytotoxic T lymphocytes through inhibition of CTLA-4 interaction with B7-1 and B7-2 on antigen-presenting dendritic cells, thereby increasing CD28 co-stimulatory activity and/or reducing CTLA-4 inhibitory signaling. Note that tumor peptide antigen is cross-presented to CTL by dendritic cells, and direct interaction of T cells with tumor cells may result in anergy through the T cell receptor (TCR). Cell 2015 162, 1186-1190DOI: (10.1016/j.cell.2015.08.038) Copyright © 2015 Elsevier Inc. Terms and Conditions