The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer
Open accessAbstract
Objective: Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. Design: Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively. In vivo efficacy and mechanistic studies were conducted with antibodies (Abs) targeting IL-6, PD-L1, CD4 or CD8 in subcutaneous or orthotopic models using Panc02, MT5 or KPC-luc cell lines; and the aggressive, genetically engineered PDAC model (Kras LSL−G12D , Trp53 LSL−R270H , Pdx1-cre, Brca2 F/F (KPC-Brca2 mice)). Systemic and local changes in immunophenotype were measured by flow cytometry or immunohistochemical analysis. Results: PSCs (n=12) demonstrated prominent IL-6 expression, which was localised to stroma of tumours. Combined IL-6 and PD-L1 blockade elicited efficacy in mice bearing subcutaneous MT5 (p<0.02) and Panc02 tumours (p=0.046), which was accompanied by increased intratumoural effector T lymphocytes (CD62L − CD44 − ). CD8-depleting but not CD4-depleting Abs abrogated the efficacy of combined IL-6 and PD-L1 blockade in mice bearing Panc02 tumours (p=0.0016). This treatment combination also elicited significant antitumour activity in mice bearing orthotopic KPC-luc tumours and limited tumour progression in KPC-Brca2 mice (p<0.001). Histological analysis revealed increased T-cell infiltration and reduced α-smooth muscle actin cells in tumours from multiple models. Finally, IL-6 and PD-L1 blockade increased overall survival in KPC-Brca2 mice compared with isotype controls (p=0.0012). Conclusions: These preclinical results indicate that targeted inhibition of IL-6 may enhance the efficacy of anti-PD-L1 in PDAC.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231
The pro- and anti-inflammatory properties of the cytokine interleukin-6
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.034 · Cited by 3,212
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681
Organoid models of human and mouse ductal pancreatic cancer
Boj, S. F., Hwang, C.-I., Baker, L. A., Chio, I. I. C., Engle, D. D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.021 · Cited by 2,150
Feig, C., Jones, J. O., Kraman, M., Wells, R. J. B., Deonarine, A., Chan, D. S., Connell, C. M., Roberts, E. W., Zhao, Q., Caballero, O. L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320318110 · Cited by 2,100
Bayne, L. J., Beatty, G. L., Jhala, N., Clark, C. E., Rhim, A. D., Stanger, B. Z., & Vonderheide, R. H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.025 · Cited by 947
STAT3 Plays a Critical Role in KRAS -Induced Pancreatic Tumorigenesis
Corcoran, R. B., Contino, G., Deshpande, V., Tzatsos, A., Conrad, C., Benes, C. H., Levy, D. E., Settleman, J., Engelman, J. A., & Bardeesy, N. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0908 · Cited by 413
STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor
Wang, Y., van Boxel-Dezaire, A. H. H., Cheon, H., Yang, J., & Stark, G. R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315862110 · Cited by 327
Fearon, D. T. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0002 · Cited by 288
Sartor, M. A., Tomlinson, C. R., Wesselkamper, S. C., Sivaganesan, S., Leikauf, G. D., & Medvedovic, M. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-538 · Cited by 263
Research works printed but not linked: 40
- 10.1158/0008-5472.CAN-14-0155 · DOI · Paper page
- 10.1016/S0140-6736(10)62307-0 · DOI · Paper page
- Al-Hajeili, 2014, Nab-paclitaxel: potential for the treatment of advanced pancreatic cancer, Onco Targets Ther, 7, 187
- 10.1158/0008-5472.CAN-13-1558-T · DOI · Paper page
- 10.1016/j.ccr.2011.03.009 · DOI · Paper page
- 10.1189/jlb.1105674 · DOI · Paper page
- 10.1016/j.smim.2014.01.008 · DOI · Paper page
- 10.1158/1538-7445.AM2011-5020 · DOI
- 10.1016/S0016-5085(03)01064-3 · DOI · Paper page
- 10.1007/s00262-011-1028-0 · DOI · Paper page
- 10.1007/s00262-014-1618-8 · DOI
- 10.1007/s00262-011-1029-z · DOI
- 10.4161/onci.24891 · DOI
- 10.1002/ijc.29445 · DOI
- 10.1158/1078-0432.CCR-15-1732 · DOI
- 10.1158/1078-0432.CCR-12-2731 · DOI · Paper page
- 10.1172/JCI80011 · DOI · Paper page
- 10.1084/jem.192.7.1027 · DOI · Paper page
- 10.1182/blood-2006-12-062422 · DOI · Paper page
- 10.1016/j.coi.2011.12.009 · DOI · Paper page
- 10.1182/blood-2007-02-072587 · DOI · Paper page
- 10.1016/j.immuni.2010.05.010 · DOI · Paper page
- 10.1158/2326-6066.CIR-13-0030 · DOI
- 10.1158/0008-5472.CAN-12-4479 · DOI · Paper page
- 10.1038/sj.onc.1204512 · DOI
- 10.1007/s00262-011-1034-2 · DOI
- 10.1214/07-AOAS102 · DOI · Paper page
- 10.1006/jmcc.1998.0655 · DOI · Paper page
- 10.18632/oncotarget.4359 · DOI
- 10.1371/journal.pone.0027729 · DOI
- 10.1007/s12185-015-1743-y · DOI
- 10.1182/blood-2013-12-546374 · DOI
- 10.1111/j.1365-2141.2010.08533.x · DOI
- 10.1093/annonc/mdv309 · DOI · Paper page
- 10.1136/gut.2010.226092 · DOI · Paper page
- 10.1158/0008-5472.CAN-14-3041 · DOI · Paper page
- 10.1016/j.ccr.2014.04.021 · DOI · Paper page
- 10.1073/pnas.1411679111 · DOI · Paper page
- 10.4049/jimmunol.170.9.4457 · DOI · Paper page
- Vassilakopoulou, 2015, Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma, Clin Cancer Res, ;22, 704
Cited by
Targeting the IL-6/JAK/STAT3 signalling axis in cancer
Johnson, D. E., O'Keefe, R. A., & Grandis, J. R. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.8 · Cited by 3,110
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Öhlund, D., Handly-Santana, A., Biffi, G., Elyada, E., Almeida, A. S., Ponz-Sarvise, M., Corbo, V., Oni, T. E., Hearn, S. A., Lee, E. J., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162024 · Cited by 2,590
Mao, X., Xu, J., Wang, W., Liang, C., Hua, J., Liu, J., Zhang, B., Meng, Q., Yu, X., & Shi, S. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01428-1 · Cited by 2,290
Biffi, G., Oni, T. E., Spielman, B., Hao, Y., Elyada, E., Park, Y., Preall, J., & Tuveson, D. A. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0710 · Cited by 1,360
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265
Metadata
- Authors
- Mace, T. A., Shakya, R., Pitarresi, J. R., Swanson, B., McQuinn, C. W., Loftus, S., Nordquist, E., Cruz-Monserrate, Z., Yu, L., Young, G., Zhong, X., Zimmers, T. A., Ostrowski, M. C., Ludwig, T., Bloomston, M., Bekaii-Saab, T., & Lesinski, G. B.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2016-10-21
- Volume
- 67
- Issue
- 2
- Pages
- 320-332
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2537220355
- Cited by
- 539
- References
- 10
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- Funders
- Lustgarten Foundation
- National Institutes of Health
- American-Italian Cancer Foundation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer. https://app.cochat.ai/papers/10.1136/gutjnl-2016-311585
- The paper
- Mace, T. A., Shakya, R., Pitarresi, J. R., Swanson, B., McQuinn, C. W., Loftus, S., Nordquist, E., Cruz-Monserrate, Z., Yu, L., Young, G., Zhong, X., Zimmers, T. A., Ostrowski, M. C., Ludwig, T., Bloomston, M., Bekaii-Saab, T., & Lesinski, G. B. (2018). IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer. Gut. https://doi.org/10.1136/gutjnl-2016-311585
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
