Stimulating CD27 to quantitatively and qualitatively shape adaptive immunity to cancer. (April 2017)

• Record Type: Journal Article
• Authors: Bullock, Timothy NJ
• Is Part Of: Current opinion in immunology. Volume 45(2017)
• Page Start: 82
• Page End: 88
• Publication Date: 2017-04
• Subjects: Immunology -- Periodicals; Allergy -- Periodicals; Immunology -- Abstracts -- Periodicals; Allergy -- Abstracts -- Periodicals; 616.079
• DOI: 10.1016/j.coi.2017.02.001
• Languages: English
• ISSNs: 0952-7915

Abstract

Highlights: CD27 is a critical link from activated dendritic cells to T cells and NK cells, and can be constrained by Treg pruning of its ligand, CD70. CD27 stimulation promotes both NK and T cell survival and effector functions. Greater understanding of how CD27-associated signaling pathways are integrated or regulate distinct facets of CD27 biology are needed. CD27 stimulation provides opportunities to sculpt the qualities of the immune response to a variety of therapeutic platforms. Abstract : The capacity of the immune system to recognize and respond to tumors has been appreciated for over 100 years. However, clinical success has largely depended on the elucidation of the positive and negative regulators of effector cells after their activation via the antigen cell receptor. On the one hand, effector cells upregulate checkpoint molecules that are thought to play a role in limiting immunopathology. On the other, second and third waves of costimulation are often required to promote the expansion, survival and differentiation of effector cells. While it is clear that the immune system can be unleashed by blocking checkpoint molecules, this approach is most effective when pre-existing responses exist in patients' tumors. Thus, coordinating checkpoint blockade with costimulation could potentially expand the patient population that receives benefit from cancer immunotherapy. This review will discuss how the costimulatory molecule CD27 sculpts immunity and preclinical/clinical data indicating its potential for cancer immunotherapy and its clinical translation.