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Cited by 506

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Tumor Cyclooxygenase-2/Prostaglandin E2–Dependent Promotion of FOXP3 Expression and CD4+CD25+ T Regulatory Cell Activities in Lung Cancer

Sharma, Sherven, Yang, Seok-Chul, Zhu, Li, Reckamp, Karen, Gardner, Brian, Baratelli, Felicita, Huang, Min, Batra, Raj K., Dubinett, Steven M.·2005·Cancer Research

Abstract

Cyclooxygenase (COX)-2 and its product prostaglandin (PG) E2 underlie an immunosuppressive network that is important in the pathogenesis of non–small cell lung cancer. CD4+CD25+ T regulatory (Treg) cells play an important role in maintenance of immunologic self-tolerance. CD4+CD25+ Treg cell activities increase in lung cancer and appear to play a role in suppressing antitumor immune responses. Definition of the pathways controlling Treg cell activities will enhance our understanding of limitation of the host antitumor immune responses. Tumor-derived COX-2/PGE2 induced expression of the Treg cell-specific transcription factor, Foxp3, and increased Treg cell activity. Assessment of E-prostanoid (EP) receptor requirements revealed that PGE2-mediated induction of Treg cell Foxp3 gene expression was significantly reduced in the absence of the EP4 receptor and ablated in the absence of the EP2 receptor expression. In vivo, COX-2 inhibition reduced Treg cell frequency and activity, attenuated Foxp3 expression in tumor-infiltrating lymphocytes, and decreased tumor burden. Transfer of Treg cells or administration of PGE2 to mice receiving COX-2 inhibitors reversed these effects. We conclude that inhibition of COX-2/PGE2 suppresses Treg cell activity and enhances antitumor responses.

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Registry

Crossref · 10.1158/0008-5472.can-05-0141

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Metadata

Authors
Sharma, S., Yang, S.-C., Zhu, L., Reckamp, K., Gardner, B., Baratelli, F., Huang, M., Batra, R. K., & Dubinett, S. M.
Venue
Cancer Research
Published
2005-06-15
Volume
65
Issue
12
Pages
5211-5220
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2090928408
Cited by
506
References
7
FWCI
15.68
Type
journal article
Language
en
Open access
closed

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