Abstract
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 have 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 aims to investigate exosomal PD-L1 in improving its predictive value and efficacy. A total of 44 patients of advanced tumors of several types, treated with anti-PD-1 therapy, were enrolled. Exosomes were collected and purified from plasma. The exosomal PD-L1 was detected with ELISA. The cytokines were measured with the MILLIPLEX magnetic bead assay. Compared to the responders, exosomal PD-L1 of the non-responders was significantly higher than that of the responders (P = 0.010) before the treatment. Concurrently, exosomal PD-L1 and tumor burden decreased when the therapy was effective. And, the baseline expression of CD28 was higher in the responders than that in the non-responders (P = 0.005). Univariate and multivariate analyses validated with 1,000 times bootstrapping suggested that high exosomal PD-L1 and low CD28 expressions were negative factors for progression-free survival (PFS) of the 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 of no 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.
Highlights
Nowadays, immunotherapy has become the focus and innovation in anti-tumor therapy [1,2,3]
Exosomes were confirmed to exist in the plasma by Western blotting, electron microscope, Nanosight and flow cytometry (Figures 2A–D), programmed cell death-1 (PD-1) and PDL1 were detected on exosomes by Western blotting and flow cytometry (Figures 2A,D)
Based on the current study, the data revealed that exosomal PD-L1 combined with CD28 from serum could serve as an effective biomarker to predict anti-PD-1 treatment response
Summary
Immunotherapy has become the focus and innovation in anti-tumor therapy [1,2,3]. The interaction between programmed cell death-1 (PD-1) and its ligand (PD-L1) exerts a considerable effect on immune escape, tumor progression, and metastasis [4]. Various types of immunotherapy, such as immune checkpoint blockade, have been used in numerous clinical trials and approved for the treatment, irrespective of the tumor types [5, 6]. PD-1 monoclonal antibody, an immune checkpoint blockade, induces an antitumor immune response by blocking the connection between PD-1 and PD-L1. Anti-PD-1 Therapy Response Prediction antibody is only 10–25% [7, 8]. Finding the novel biomarkers for predicting the efficacy of anti-PD-1 treatment is an urgent requisite
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