Abstract：
:Targeting immune checkpoint receptors has emerged as an effective strategy to induce immune-mediated cancer regression in the subset of patients who have significant pre-existing anti-tumor immunity. For the remainder, effective anti tumor responses may require vaccination. Radiotherapy, traditionally used to achieve local tumor control, has acquired a new role, that of a partner for immunotherapy. Ionizing radiation has pro-inflammatory effects that facilitate tumor rejection. Radiation alters the tumor to enhance the concentration of effector T cells via induction of chemokines, cytokines and adhesion molecules. In parallel, radiation can induce an immunogenic death of cancer cells, promoting cross-presentation of tumor-derived antigens by dendritic cells to T cells. Newly generated anti-tumor immune responses have been demonstrated post-radiation in both murine models and occasional patients, supporting the hypothesis that the irradiated tumor can become an in situ vaccine. It is in this role, that radiation can be applied to induce anti-tumor T cells in lymphocyte-poor tumors, and possibly benefit patients who would otherwise fail to respond to immune checkpoint inhibitors. This review summarizes preclinical and clinical data demonstrating that radiation acts in concert with antibodies targeting the immune checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4), to induce therapeutically effective anti-tumor T cell responses in tumors otherwise non responsive to anti-CTLA-4 therapy.
journal_name
Vaccinejournal_title
Vaccineauthors
Vanpouille-Box C,Pilones KA,Wennerberg E,Formenti SC,Demaria Sdoi
10.1016/j.vaccine.2015.05.105subject
Has Abstractpub_date
2015-12-16 00:00:00pages
7415-7422issue
51eissn
0264-410Xissn
1873-2518pii
S0264-410X(15)00911-1journal_volume
33pub_type
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