Anti-PD-1 Therapy Response Predicted by the Combination of Exosomal PD-L1 and CD28
Open accessAbstract
Anti-PD-1 therapy has been approved for cancer treatment. However, the response rate is unsatisfactory. The expression of PD-L1 in tumor tissues is unreliable to predict the treatment response. Recent studies suggested that exosomal PD-L1 not only exerts immunosuppressive effects but also plays a significant role in the development of tumor microenvironment. Thus, the present study aimed to investigate exosomal PD-L1 in improving its predictive value and efficacy. A total of 44 patients with several types of advanced tumors, treated by anti-PD-1 therapy, were enrolled. Exosomes were collected and purified from plasma. The exosomal PD-L1 was detected by ELISA. The cytokines were measured by the MILLIPLEX magnetic bead assay. Compared to the responders, exosomal PD-L1 of the non-responders were significantly higher than those of the responders (P=0.010) before the treatment. Concurrently, exosomal PD-L1 and tumor burden decreased when the therapy was effective. Also, the baseline expression of CD28 was higher in the responders than non-responders (P=0.005). Univariate and multivariate analysis validated with 1000 times bootstrapping suggested that high exosomal PD-L1 and low CD28 expression were negative factors for progression-free survival (PFS) in patients who underwent anti-PD-1 treatment. The combination of exosomal PD-L1 and CD28 obtained more area under the curve (AUC) of receiver operating characteristic (ROC) (AUC 0.850 vs. 0.784 vs. 0.678) and showed a higher probability without progression via nomograph. These findings suggested that the expression of exosomal PD-L1 and CD28 could serve as the predictive biomarkers for clinical responses to anti-PD-1 treatment.
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Exosomal PD-L1 combined with CD28 has high predictive value, with an area under the curve of 0.85.
“A high predictive value has also been demonstrated for exosomal PD-L1 in combination with CD28 (area under curve of 0.85)”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Zhang et al., 2020
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Self-citation
- Authors
- Zhang, C., Fan, Y., Che, X., Zhang, M., Li, Z., Li, C., Wang, S., Wen, T., Hou, K., Shao, X., Liu, Y., & Qu, X.
- Affiliations
- First Hospital of China Medical University (CN)
- Corresponding author
- Qu, Xiujuan
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2020-05-27
- Volume
- 10
- Pages
- 760-760
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC7266952
- OpenAlex
- W3030731299
- Cited by
- 69
- References
- 47
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 19 · 2023: 10 · 2022: 12 · 2021: 9 · 2020: 3 · 2019: 1
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- SSRN Electronic Journal (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Major Science and Technology Projects of China (2017ZX09304025)
- National Natural Science Foundation of China (31770963, 81602098)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- anti-PD-1 therapy, exosomal PD-L1, CD28, predictive biomarkers, treatment response prediction, exosomes, plasma exosomes, tumor microenvironment, progression-free survival, advanced cancer, immune checkpoint inhibitors
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