Therapeutic efficacy of 4-1BB costimulation is abrogated by PD-1 blockade in a model of spontaneous B-cell lymphoma

McKee, Sara J., Doff, Brianna L., Soon, Megan S. F. and Mattarollo, Stephen R. (2017) Therapeutic efficacy of 4-1BB costimulation is abrogated by PD-1 blockade in a model of spontaneous B-cell lymphoma. Cancer Immunology Research, 5 3: 191-197. doi:10.1158/2326-6066.CIR-16-0249


Author McKee, Sara J.
Doff, Brianna L.
Soon, Megan S. F.
Mattarollo, Stephen R.
Title Therapeutic efficacy of 4-1BB costimulation is abrogated by PD-1 blockade in a model of spontaneous B-cell lymphoma
Journal name Cancer Immunology Research   Check publisher's open access policy
ISSN 2326-6074
2326-6066
Publication date 2017-03-01
Sub-type Article (original research)
DOI 10.1158/2326-6066.CIR-16-0249
Open Access Status Not yet assessed
Volume 5
Issue 3
Start page 191
End page 197
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2018
Language eng
Formatted abstract
Combinations of mAbs that target various components of T-cell activation/inhibition may work synergistically to improve antitumor immunity against cancer. In this study, we investigated the therapeutic potential of combining an anticancer vaccination strategy with antibodies targeting an immune stimulatory (4-1BB) and immune inhibitory (PD-1) receptor, in a preclinical model of spontaneously arising c-Myc–driven B-cell lymphoma. In Eμ-myc transgenic mice, we reveal that 4-1BB agonistic mAb treatment alone was sufficient to drive antitumor immunity and prevent disease progression in 70% of mice. When combined with an α-GalCer–loaded, irradiated tumor cell vaccine, 4-1BB mAb treatment led to increased expansion of effector CD8 T-cell populations and protection of long-term surviving mice against tumor rechallenge. Unexpectedly, PD-1 blockade did not provide therapeutic benefit. The T-cell–promoting effects and antitumor activity of 4-1BB mAb were diminished when used simultaneously with a PD-1–blocking mAb. This was associated with a rapid and dramatic reduction in effector CD8+ T-cell subsets in the presence of PD-1 blockade. These findings reveal that supporting T-cell activation therapeutically is effective for controlling B-cell lymphomas; however, caution is required when combining antibody-mediated modulation of both costimulatory and coinhibitory T-cell receptors.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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