A prime/boost vaccine platform efficiently identifies CD27 agonism and depletion of myeloid-derived suppressor cells as therapies that rationally combine with checkpoint blockade in ovarian cancer
Open accessAbstract
Cancer immunotherapies have generated remarkable clinical responses for some patients with advanced/metastatic disease, prompting exploration of rational combination therapies to bolster anti-tumor immunity in patients with limited response or those who experience tumor progression following an initial response to immunotherapy. In contrast to other tumor indications, objective response rates to single-agent PD-1/PD-L1 blockade in ovarian cancer are limited, suggesting a need to identify combinatorial approaches that lead to tumor regression in a setting where checkpoint blockade alone is ineffective. Using a pre-clinical model of aggressive intraperitoneal ovarian cancer, we have previously reported on a heterologous prime/boost cancer vaccine that elicits robust anti-tumor immunity, prolongs survival of tumor-bearing mice, and which is further improved when combined with checkpoint blockade. As tumor control in this model is CD8 + T cell dependent, we reasoned that the prime/boost vaccine platform could be used to explore additional treatment combinations intended to bolster the effects of CD8 + T cells. Using whole tumor transcriptomic data, we identified candidate therapeutic targets anticipated to rationally combine with prime/boost vaccination. In the context of a highly effective cancer vaccine, CD27 agonism or antibody-mediated depletion of granulocytic cells each modestly increased tumor control following vaccination, with anti-PD-1 therapy further improving treatment efficacy. These findings support the use of immunotherapies with well-defined mechanisms(s) of action as a valuable platform for identifying candidate combination approaches for further therapeutic testing in ovarian cancer.
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
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A series of preclinical studies showed that co-stimulatory molecule agonists improved α-PD-1/PD-L1 efficacy.
“A series of preclinical studies showed that co-stimulatory molecule agonists improved α-PD-1/PD-L1 efficacy [170–176].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [170]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
An immunogenic personal neoantigen vaccine for patients with melanoma
Ott, P. A., Hu, Z., Keskin, D. B., Shukla, S. A., Sun, J., Bozym, D. J., Zhang, W., Luoma, A., Giobbie-Hurder, A., Peter, L., et al. (2017) · Nature · doi:10.1038/nature22991 · Cited by 2,936 · see citing works
Sato, E., Olson, S. H., Ahn, J., Bundy, B. N., Nishikawa, H., Qian, F., Jungbluth, A. A., Frosina, D., Gnjatic, S., Ambrosone, C. B., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509182102 · Cited by 2,375 · see citing works
Self-citationTumour-intrinsic resistance to immune checkpoint blockade
Kalbasi, A. K., & Ribas, A. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0218-4 · Cited by 1,491 · see citing works
Mechanisms of resistance to immune checkpoint inhibitors
Jenkins, R. W., Barbie, D. A., & Flaherty, K. T. (2018) · British Journal of Cancer · doi:10.1038/bjc.2017.434 · Cited by 1,383 · see citing works
Lundegaard, C., Lamberth, K., Harndahl, M. N., Buus, S., Lund, O., & Nielsen, M. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn202 · Cited by 808 · see citing works
Evolving synergistic combinations of targeted immunotherapies to combat cancer
Melero, I., Berman, D. M., Aznar, M. A., Korman, A. J., Perez‐Gracia, J. L., & Haanen, J. B. A. G. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3973 · Cited by 633 · see citing works
PD-L1 on host cells is essential for PD-L1 blockade–mediated tumor regression
Tang, H., Liang, Y., Anders, R. A., Taube, J. M., Qiu, X., Mulgaonkar, A., Liu, X., Harrington, S. M., Guo, J., Xin, Y., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96061 · Cited by 520 · see citing works
Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation.
Hintzen, R. Q., Lens, S. M. A., Lammers, K. M., Kuiper, H., Beckmann, M. P., & van Lier, R. A. W. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.6.2612 · Cited by 244 · see citing works
Odunsi, K. O., Matsuzaki, J., Karbach, J., Neumann, A., Mhawech-Fauceglia, P. Y., Miller, A., Beck, A. F., Morrison, C. D., Ritter, G., Godoy, H. E., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1117208109 · Cited by 200 · see citing works
Self-citationEpigenetic Potentiation of NY-ESO-1 Vaccine Therapy in Human Ovarian Cancer
Odunsi, K. O., Matsuzaki, J., James, S. R., Mhawech-Fauceglia, P. Y., Tsuji, T., Miller, A., Zhang, W., Akers, S. N., Griffiths, E. A., Miliotto, A. J., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0126 · Cited by 193 · see citing works
Self-citationNew emerging targets in cancer immunotherapy: CD27 (TNFRSF7)
Starzer, A. M., & Berghoff, A. S. (2019) · ESMO Open · doi:10.1136/esmoopen-2019-000629 · Cited by 168 · see citing works
Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment
Singel, K. L., Emmons, T. R., Khan, A. N. H., Mayor, P. C., Shen, S., Wong, J. T., Morrell, K., Eng, K. H., Mark, J., Bankert, R. B., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.122311 · Cited by 140 · see citing works
Self-citationTuning the Tumor Myeloid Microenvironment to Fight Cancer
Jahchan, N. S., Mujal, A. M., Pollack, J. L., Binnewies, M., Sriram, V., Reyno, L. M., & Krummel, M. F. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01611 · Cited by 120 · see citing works
Ribechini, E., Leenen, P. J. M., & Lutz, M. B. (2009) · European Journal of Immunology · doi:10.1002/eji.200939530 · Cited by 92 · see citing works
Efficient identification of neoantigen-specific T-cell responses in advanced human ovarian cancer
Liu, S., Matsuzaki, J., Wei, L., Tsuji, T., Battaglia, S., Hu, Q., Cortes, E., Wong, L.-P., Yan, L., Long, M. D., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0629-6 · Cited by 84 · see citing works
Self-citationNY-ESO-1 expression predicts an aggressive phenotype of ovarian cancer
Szender, J. B., Papanicolau‐Sengos, A., Eng, K. H., Miliotto, A. J., Lugade, A. A., Gnjatic, S., Matsuzaki, J., Morrison, C. D., & Odunsi, K. O. (2017) · Gynecologic Oncology · doi:10.1016/j.ygyno.2017.03.509 · Cited by 75 · see citing works
Self-citationCancer Vaccines in Ovarian Cancer: How Can We Improve?
Lluesma, S. M., Wolfer, A., Harari, A., & Kandalaft, L. E. (2016) · Biomedicines · doi:10.3390/biomedicines4020010 · Cited by 59 · see citing works
McGray, A. R., Huang, R.-Y., Battaglia, S., Eppolito, C., Miliotto, A. J., Stephenson, K. B., Lugade, A. A., Webster, G., Lichty, B. D., Seshadri, M., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0641-x · Cited by 54 · see citing works
Self-citationImmunotherapy with checkpoint inhibitors in patients with ovarian cancer: Still promising?
González-Martı́n, A., & Sánchez‐Lorenzo, L. (2019) · Cancer · doi:10.1002/cncr.32520 · Cited by 51 · see citing works
Sanborn, R. E., Pishvaian, M. J., Callahan, M. K., Weise, A. M., Sikic, B. I., Rahma, O. E., Cho, D. C., Rizvi, N. A., Bitting, R. L., Starodub, A., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.3001 · Cited by 18 · see citing works
Self-citationNakhoda, S. K., & Olszanski, A. J. (2020) · Pharmaceutical Medicine · doi:10.1007/s40290-020-00326-z · Cited by 17 · see citing works
Adaptive Resistance to Cancer Immunotherapy
McGray, A. R., & Bramson, J. L. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-67577-0_14 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445 · see citing works
Here, There, and Everywhere: Myeloid-Derived Suppressor Cells in Immunology
Ostrand‐Rosenberg, S., Lamb, T. J., & Pawelec, G. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2200914 · Cited by 58 · see citing works
Franzese, O. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312848 · Cited by 28 · see citing works
Zhao, L., Chen, X., Wu, H., He, Q., Ding, L., & Yang, B. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115724 · Cited by 24 · see citing works
Recent advances in understanding the immune microenvironment in ovarian cancer
Chen, J., Yang, L., Ma, Y., & Zhang, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1412328 · Cited by 18 · see citing works
Bachmann, C. (2023) · Cancers · doi:10.3390/cancers15225356 · Cited by 17 · see citing works
Świderska, J., Kozłowski, M., Gaur, M., Pius‐Sadowska, E., Kwiatkowski, S., Machaliński, B., & Cymbaluk‐Płoska, A. (2022) · Diagnostics · doi:10.3390/diagnostics12020251 · Cited by 16 · see citing works
Mark, J., Fisher, D. T., Kim, M., Emmons, T. R., Khan, A. N. M. N., Alqassim, E., Singel, K. L., Mistarz, A., Lugade, A. A., Zhan, H., et al. (2022) · Gynecologic Oncology · doi:10.1016/j.ygyno.2022.11.001 · Cited by 7 · see citing works
Self-citationGuo, Y. C., Yang, N., Li, G., Yin, X., & Dong, L. (2022) · Journal of Immunology Research · doi:10.1155/2022/4379216 · Cited by 4 · see citing works
Chiello, J. L., Shaikh, N., Jacobi, J. J., Gaulin, N., Santos, G. S., Keck, C., Hess, S. M., Lichty, B. D., Singh, P. K., Rosario, S. R., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.09.047 · Cited by 3 · see citing works
Self-citationSun, J., Feng, Q., Xu, Y., Liu, P., & Wu, Y. (2024) · Journal of Ovarian Research · doi:10.1186/s13048-024-01426-z · Cited by 3 · see citing works
Comprehensive Analysis of Expression and Pathway for CD27 in Esophageal Cancer
Xiao, F., & Wang, L. (2023) · Molecular Biotechnology · doi:10.1007/s12033-023-00850-8
- Authors
- McGray, A. J. R., Eppolito, C., Miliotto, A., Singel, K. L., Stephenson, K., Lugade, A., Segal, B. H., Keler, T., Webster, G., Lichty, B., Kozbor, D., & Odunsi, K.
- Affiliations
- Roswell Park Comprehensive Cancer Center (US)
- McMaster University (CA)
- Celldex Therapeutics (United States) (US)
- Corresponding author
- Odunsi, K.
- Venue
- Cancer Immunology, Immunotherapy
- Published
- 2021-04-20
- Volume
- 70
- Issue
- 12
- Pages
- 3451-3460
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC8057655
- OpenAlex
- W3155027568
- Cited by
- 12
- References
- 22
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 4 · 2022: 4
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Immunology Immunotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ovarian Cancer Research Fund (326870)
- Roswell Park Cancer Institute
- National Institutes of Health (P50CA159981-01A1, UO1 CA233085-01A1, R01CA188900, P30CA016056, R03CA223623)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Keywords
- ovarian cancer, myeloid-derived suppressor cells, PD-1/PD-L1 blockade, combination immunotherapy, CD8+ T cells, cancer transcriptomics, drug target identification
- MeSH terms
- Myeloid-Derived Suppressor Cells, Immune Checkpoint Inhibitors, Animals, Combined Modality Therapy, Female, Immunotherapy, Ovarian Neoplasms, Tumor Necrosis Factor Receptor Superfamily, Member 7, CD8-Positive T-Lymphocytes, Cancer Vaccines, Mice, Programmed Cell Death 1 Receptor
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
