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Cited by 398

The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.

PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors

Open access
Soares, Kevin C., Rucki, Agnieszka A., Wu, Annie A., Olino, Kelly, Xiao, Qian, Chai, Yi, Wamwea, Anthony, Bigelow, Elaine, Lutz, Eric, Liu, Linda, Yao, Sheng, Anders, Robert A., Laheru, Daniel, Wolfgang, Christopher L., Edil, Barish H., Schulick, Richard D., Jaffee, Elizabeth M., Zheng, Lei·2015·Journal of Immunotherapy
DOI 10.1097/cji.0000000000000062
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Abstract

Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis due to late detection and resistance to conventional therapies. Published studies show that the PDA tumor microenvironment is predominantly infiltrated with immune suppressive cells and signals that if altered, would allow effective immunotherapy. However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. We recently reported that inhibition of the CTLA-4 pathway when given together with a T cell inducing vaccine gives objective responses in metastatic PDA patients. In this study, we evaluated blockade of the PD-1/PD-L1 pathway. We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. In addition, combination therapy with vaccine and PD-1 antibody blockade improved murine survival compared with PD-1 antibody monotherapy or GVAX therapy alone. Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-γ production of CD8 T cells in the tumor microenvironment. Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment.

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Metadata

Authors
Soares, K. C., Rucki, A. A., Wu, A. A., Olino, K., Xiao, Q., Chai, Y., Wamwea, A., Bigelow, E., Lutz, E., Liu, L., Yao, S., Anders, R. A., Laheru, D., Wolfgang, C. L., Edil, B. H., Schulick, R. D., Jaffee, E. M., & Zheng, L.
Venue
Journal of Immunotherapy
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-01
Volume
38
Issue
1
Pages
1-11
ISSN
1524-9557 (ISSN-L)
DOI
10.1097/cji.0000000000000062
OpenAlex
W2086526310
Cited by
398
References
59
FWCI
16.37
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors. https://app.cochat.ai/papers/10.1097/cji.0000000000000062
The paper
Soares, K. C., Rucki, A. A., Wu, A. A., Olino, K., Xiao, Q., Chai, Y., Wamwea, A., Bigelow, E., Lutz, E., Liu, L., Yao, S., Anders, R. A., Laheru, D., Wolfgang, C. L., Edil, B. H., Schulick, R. D., Jaffee, E. M., & Zheng, L. (2015). PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors. Journal of Immunotherapy. https://doi.org/10.1097/cji.0000000000000062

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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