Control of established melanoma by CD27 stimulation is associated with enhanced effector function and persistence, and reduced PD-1 expression of tumor infiltrating CD8(+) T cells
Control of established melanoma by CD27 stimulation is associated with enhanced effector function and persistence, and reduced PD-1 expression of tumor infiltrating CD8(+) T cells
The immune response to the tumor can be enhanced by targeting costimulatory molecules on T cells. As the CD70-CD27 costimulatory axis plays an important role in the activation, survival, and differentiation of lymphocytes, we have examined the efficacy of agonistic anti-CD27 antibodies as monotherapies for established melanoma in a murine model. We show that this approach leads to a substantial reduction in the outgrowth of both experimental lung metastases and subcutaneous tumors. Anti-CD27 treatment supports the maintenance of tumor-specific CD8(+) T cells within the tumor, reduces the frequency of FoxP3-expressing CD4(+) T cells within tumors, and potentiates the ability of NK1.1(+) and CD8(+) tumor infiltrating cells to secrete IFN? upon coculture with tumor cells. The enhanced effector function correlated with lower levels of PD-1 expression on CD8(+) T cells from anti-CD27-treated mice. Despite the modulating effect of anti-CD27 on multiple cell types, only CD8(+) T cells were absolutely required for tumor control. The CD4(+) T cells were dispensable, whereas NK1.1(+) cells were needed during early stages of tumor growth but not for the effectiveness of anti-CD27. Thus, CD27-mediated costimulation provides a potent boost to multiple aspects of the endogenous responses to tumor, and may be exploited to enhance tumor immunity.
769-779
Roberts, D.J.
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Franklin, N.A.
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Kingeter, L.M.
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Yagita, H.
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Tutt, Alison L
46ce577b-aea1-412d-84ea-fc4dab794469
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Bullock, T.N.
e70e88b6-76e5-4b55-8b9b-7663e16f1965
October 2010
Roberts, D.J.
8061ca02-52f2-4a18-b540-c7f1e2838341
Franklin, N.A.
109cd014-54bb-4b14-b53e-911bdcc73035
Kingeter, L.M.
fe3e8b10-f292-4f7e-abf1-7319aae1ee22
Yagita, H.
283267c4-9862-4a3e-973c-1ef5db522195
Tutt, Alison L
46ce577b-aea1-412d-84ea-fc4dab794469
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Bullock, T.N.
e70e88b6-76e5-4b55-8b9b-7663e16f1965
Roberts, D.J., Franklin, N.A., Kingeter, L.M., Yagita, H., Tutt, Alison L, Glennie, Martin J. and Bullock, T.N.
(2010)
Control of established melanoma by CD27 stimulation is associated with enhanced effector function and persistence, and reduced PD-1 expression of tumor infiltrating CD8(+) T cells.
Journal of Immunotherapy, 33 (8), Winter Issue, .
(doi:10.1097/CJI.0b013e3181ee238f).
(PMID:20842060)
Abstract
The immune response to the tumor can be enhanced by targeting costimulatory molecules on T cells. As the CD70-CD27 costimulatory axis plays an important role in the activation, survival, and differentiation of lymphocytes, we have examined the efficacy of agonistic anti-CD27 antibodies as monotherapies for established melanoma in a murine model. We show that this approach leads to a substantial reduction in the outgrowth of both experimental lung metastases and subcutaneous tumors. Anti-CD27 treatment supports the maintenance of tumor-specific CD8(+) T cells within the tumor, reduces the frequency of FoxP3-expressing CD4(+) T cells within tumors, and potentiates the ability of NK1.1(+) and CD8(+) tumor infiltrating cells to secrete IFN? upon coculture with tumor cells. The enhanced effector function correlated with lower levels of PD-1 expression on CD8(+) T cells from anti-CD27-treated mice. Despite the modulating effect of anti-CD27 on multiple cell types, only CD8(+) T cells were absolutely required for tumor control. The CD4(+) T cells were dispensable, whereas NK1.1(+) cells were needed during early stages of tumor growth but not for the effectiveness of anti-CD27. Thus, CD27-mediated costimulation provides a potent boost to multiple aspects of the endogenous responses to tumor, and may be exploited to enhance tumor immunity.
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Published date: October 2010
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Local EPrints ID: 169243
URI: http://eprints.soton.ac.uk/id/eprint/169243
ISSN: 1524-9557
PURE UUID: f15b9df0-3142-4769-9d26-cec44bf2bbea
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Date deposited: 13 Dec 2010 11:37
Last modified: 14 Mar 2024 02:20
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Author:
D.J. Roberts
Author:
N.A. Franklin
Author:
L.M. Kingeter
Author:
H. Yagita
Author:
Alison L Tutt
Author:
T.N. Bullock
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