ArticleCancer medicine2023
Immune-independent acquired resistance to PD-L1 antibody initiated by PD-L1 upregulation via PI3K/AKT signaling can be reversed by anlotinib.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Anlotinib plus whole-brain radiotherapy for NSCLC brain metastases: a prospective, non-randomized, single-center cohort study.Scientific reports · 2026Article
- Berberine induces PD-L1 degradation via the autophagy-lysosome pathway through the PI3K-Akt pathway and enhances immunogenic cell death in triple-negative breast cancer.Frontiers in immunology · 2026Article
- Cancer immunoediting in the melanoma tumor microenvironment: from immune elimination to therapeutic resistance.Frontiers in immunology · 2026Review
- EZH2 Inhibition in Mesothelioma Cells Increases the Release of Extracellular Vesicles That Skew Neutrophils Toward a Protumor Phenotype.International journal of molecular sciences · 2025Article
- Parkinson's disease: exploring the systemic immune mechanisms through molecular investigations.Inflammopharmacology · 2025Review
- Targeting PD-L1 for PCNS-DLBCL: from molecular effects to clinical translation.Frontiers in immunology · 2025Review
- Sequential anlotinib and camrelizumab combination therapy achieves exceptional survival in multi-driver mutated, TMB-low/PD-L1-low/MSS pulmonary sarcomatoid carcinoma: case report and literature review.Frontiers in immunology · 2025Review
- Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy.International journal of nanomedicine · 2024Review
- Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion.International journal of molecular sciences · 2023Article
- Immune-independent acquired resistance to PD-L1 antibody initiated by PD-L1 upregulation via PI3K/AKT signaling can be reversed by anlotinib.Cancer medicine · 2023Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the benefit with cancer immunotherapies in clinical implication, immunotherapeutic resistance occurred in many patients and the mechanism remains unknown. Increasing evidence has revealed that cell-intrinsic programmed cell death ligand 1 (PD-L1) may play a non-negotiable part in immunotherapeutic resistance. Our present study aimed to elucidate the immune-independent acquired resistance mechanism to PD-L1 antibody. We found elevated PD-L1 expression induced by PD-L1 antibodies in cancer cell and vascular endothelial cells (VECs) with substantially acquired resistance to PD-L1 antibodies. Moreover, proliferation of resistant cells was accelerated and the apoptosis was reduced in the absence of immune compared with parental cells. Subsequently, we confirmed that the activation of the PI3K/AKT pathway is involved in the upregulation of PD-L1 expression. Finally, we found that low dose of anlotinib downregulated PD-L1 expression only in VECs via inhibiting the PI3K/AKT pathway; however, the same effect was not observed in cancer cells. To sum up, our findings revealed that upregulation of PD-L1 via activation of the PI3K/AKT signal pathway may promote acquired resistance to PD-L1 antibodies in an immune-independent manner. SIGNIFICANCE: These findings provide new mechanisms of immunotherapeutic resistance and effective evidence of anlotinib combined with immunotherapy.
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