Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function
Chen EP, Markosyan N, Connolly E, Lawson JA, Li X, Grant GR, Grosser T, FitzGerald GA, Smyth EM (2014)
Carcinogenesis 35(8): 1788-1797.
Zeitschriftenaufsatz
| Veröffentlicht | Englisch
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Autor*in
Chen, Edward P.;
Markosyan, Nune;
Connolly, Emma;
Lawson, John A.;
Li, Xuanwen;
Grant, Gregory R.;
Grosser, TiloUniBi
;
FitzGerald, Garret A.;
Smyth, Emer M.
![](https://pub.uni-bielefeld.de/images/icon_orcid.png)
Abstract / Bemerkung
Cyclooxygenase-2 (COX-2) expression is associated with poor prognosis across a range of human cancers, including breast cancer. The contribution of tumor cell-derived COX-2 to tumorigenesis has been examined in numerous studies; however, the role of stromal-derived COX-2 is ill-defined. Here, we examined how COX-2 in myeloid cells, an immune cell subset that includes macrophages, influences mammary tumor progression. In mice engineered to selectively lack myeloid cell COX-2 [myeloid-COX-2 knockout (KO) mice], spontaneous neu oncogene-induced tumor onset was delayed, tumor burden reduced, and tumor growth slowed compared with wild-type (WT). Similarly, growth of neu-transformed mammary tumor cells as orthotopic tumors in immune competent syngeneic myeloid-COX-2 KO host mice was reduced compared with WT. By flow cytometric analysis, orthotopic myeloid-COX-2 KO tumors had lower tumor-associated macrophage (TAM) infiltration consistent with impaired colony stimulating factor-1-dependent chemotaxis by COX-2 deficient macrophages in vitro. Further, in both spontaneous and orthotopic tumors, COX-2-deficient TAM displayed lower immunosuppressive M2 markers and this was coincident with less suppression of CD8+ cytotoxic T lymphocytes (CTLs) in myeloid-COX-2 KO tumors. These studies suggest that reduced tumor growth in myeloid-COX-2 KO mice resulted from disruption of M2-like TAM function, thereby enhancing T-cell survival and immune surveillance. Antibody-mediated depletion of CD8+, but not CD4+ cells, restored tumor growth in myeloid-COX-2 KO to WT levels, indicating that CD8+ CTLs are dominant antitumor effectors in myeloid-COX-2 KO mice. Our studies suggest that inhibition of myeloid cell COX-2 can potentiate CTL-mediated tumor cytotoxicity and may provide a novel therapeutic approach in breast cancer therapy.
Erscheinungsjahr
2014
Zeitschriftentitel
Carcinogenesis
Band
35
Ausgabe
8
Seite(n)
1788-1797
ISSN
0143-3334
eISSN
1460-2180
Page URI
https://pub.uni-bielefeld.de/record/2965319
Zitieren
Chen EP, Markosyan N, Connolly E, et al. Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function. Carcinogenesis. 2014;35(8):1788-1797.
Chen, E. P., Markosyan, N., Connolly, E., Lawson, J. A., Li, X., Grant, G. R., Grosser, T., et al. (2014). Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function. Carcinogenesis, 35(8), 1788-1797. https://doi.org/10.1093/carcin/bgu053
Chen, Edward P., Markosyan, Nune, Connolly, Emma, Lawson, John A., Li, Xuanwen, Grant, Gregory R., Grosser, Tilo, FitzGerald, Garret A., and Smyth, Emer M. 2014. “Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function”. Carcinogenesis 35 (8): 1788-1797.
Chen, E. P., Markosyan, N., Connolly, E., Lawson, J. A., Li, X., Grant, G. R., Grosser, T., FitzGerald, G. A., and Smyth, E. M. (2014). Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function. Carcinogenesis 35, 1788-1797.
Chen, E.P., et al., 2014. Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function. Carcinogenesis, 35(8), p 1788-1797.
E.P. Chen, et al., “Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function”, Carcinogenesis, vol. 35, 2014, pp. 1788-1797.
Chen, E.P., Markosyan, N., Connolly, E., Lawson, J.A., Li, X., Grant, G.R., Grosser, T., FitzGerald, G.A., Smyth, E.M.: Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function. Carcinogenesis. 35, 1788-1797 (2014).
Chen, Edward P., Markosyan, Nune, Connolly, Emma, Lawson, John A., Li, Xuanwen, Grant, Gregory R., Grosser, Tilo, FitzGerald, Garret A., and Smyth, Emer M. “Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function”. Carcinogenesis 35.8 (2014): 1788-1797.
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