Journal
CURRENT OPINION IN IMMUNOLOGY
Volume 22, Issue 3, Pages 385-390Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.coi.2010.04.005
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Funding
- NIAID NIH HHS [P01 AI052271, P01 AI082282-01, U19 AI074078-04, U19 AI074078-01, P01 AI052271-01, U19 AI074078-03, U19 AI074078, P01 AI052271-03, P01 AI082282, P01 AI052271-04, U19 AI074078-02, P01 AI052271-05, P01 AI052271-02] Funding Source: Medline
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The clinical success of adaptive transfer of in vitro expanded antigen-specific CD8(+) T cells isolated from patients tumors has demonstrated that effector cells of the adaptive immune system can effectively eliminate even large tumor masses. Nevertheless, cancer vaccines that aim to expand such CD8(+) T cells in situ have had remarkably little success in spite of numerous attempts. Recent advances in basic immunology have revealed layers of complexity controlling activation and maintenance of adaptive immune responses that are tightly controlled by immunoinhibitory pathways to avoid horror autotoxicus. During tumor progression the activities of negative pathways increase and together with cancer immune evasion tactics presumably prevent induction of an efficacious immune response by cancer vaccines that solely provide more antigen to an already suppressed system. Cancer vaccines may thus need to readjust the imbalance of the cancer patients' immune system by inhibiting immunoinhibitors; such regimens have shown preclinical efficacy and are now entering clinical trials hopefully ending the Kafkaesque futility of cancer vaccines.
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