2016
DOI: 10.1146/annurev-immunol-032414-112049
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Coinhibitory Pathways in Immunotherapy for Cancer

Abstract: The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tol… Show more

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Cited by 789 publications
(810 citation statements)
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References 249 publications
(247 reference statements)
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“…The immune system plays an important role in any cancer treatment directly or indirectly (33)(34)(35)(36)(37)(38)(39). Recently, cancer immunotherapy using immune checkpoint blockers (ICBs) has revolutionized cancer therapy by curing some patients (40)(41)(42). However, the majority of cancer patients do not respond to ICBs, even in the most promising indications (41,43).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The immune system plays an important role in any cancer treatment directly or indirectly (33)(34)(35)(36)(37)(38)(39). Recently, cancer immunotherapy using immune checkpoint blockers (ICBs) has revolutionized cancer therapy by curing some patients (40)(41)(42). However, the majority of cancer patients do not respond to ICBs, even in the most promising indications (41,43).…”
Section: Discussionmentioning
confidence: 99%
“…Recently, cancer immunotherapy using immune checkpoint blockers (ICBs) has revolutionized cancer therapy by curing some patients (40)(41)(42). However, the majority of cancer patients do not respond to ICBs, even in the most promising indications (41,43). In the case of CRCs, the success of ICBs is limited to a small portion of patients with high microsatellite instability or mismatch repairdeficient cancers (44,45).…”
Section: Discussionmentioning
confidence: 99%
“…Thus, even though exhaustion is quite variable and many aspects hard to define perfectly, interrupting key points in the system can reverse the phenomenon and lead to impressive in vivo impact. Also, since the phenomenon is reproduced across so many immunologic model systems, and parallels are easily seen in human immunity, it is perhaps not surprising that reversal of exhaustion through checkpoint blockade (eg, blocking of PD‐1 interactions) has a substantial impact in certain cancers 10. It is also interesting that the biggest effects have been seen in cancers, while many of the key original discoveries were made in virology.…”
Section: Introductionmentioning
confidence: 96%
“…Through its interaction with the corresponding receptor programmed cell death protein 1 (PD-1) on the surface of immune cells, tumor PD-L1 suppresses antitumor immunity in the tumor microenvironment by multiple mechanisms including induction of T cell apoptosis and functional exhaustion. 2,4 More recent studies show that PD-L1 expressed in host immune cells including myeloid cells also contribute to suppression of antitumor immunity and immunotherapy. 57 Anti-PD-L1 and anti-PD-1 antibody immunotherapies block the immune-suppressive actions of PD-L1/PD-1 to mediate durable responses and have become standard of care for multiple cancer types.…”
Section: Introductionmentioning
confidence: 99%