Tumor‐derived exosomal PD‐L1 in progression of cancer and immunotherapy

• Published in: Journal of cellular physiology 2022-03, Vol.237 (3), p.1648-1660
• Main Authors: Rasihashemi, Seyed Z., Rezazadeh Gavgani, Erfan, Majidazar, Reza, Seraji, Parya, Oladghaffari, Mobina, Kazemi, Tohid, Lotfinejad, Parisa
• Format: Article
• Language: English
• Subjects: Antibodies; B7-H1 Antigen - metabolism; Biomarkers; Cancer; cancer progression; Cell membranes; Diagnosis; exosomal PD‐L1; Exosomes; Exosomes - metabolism; Health services; Humans; Immune checkpoint; Immune Tolerance; Immunologic Factors - pharmacology; Immunotherapy; Medical prognosis; Metastases; Neoplasms - pathology; Patients; PD-L1 protein; PD‐L1; Survival; Therapeutic targets; Therapy; Topology; Tumors; tumor‐derived exosomes
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.30645

Cancer is a gravely important health issue all over the world and has been spreading fast. In recent years immune checkpoint treatment options have been used extensively as a primary line of treatment for different cancer types. PD‐1 and its ligand, PD‐L1, are members of the immune‐checkpoints superfamily. Anti‐PD‐L1 and anti‐PD‐1 antibodies have shown efficacy against different cancer types, but fewer than 30% of patients have shown robust therapeutic responses and, therefore, it is hypothesized that exosomal PD‐L1 is the mechanism to blame for failure in primary immune checkpoint therapy. The identical membrane topology of exosomal PD‐L1 with tumor cell membrane‐type provides the possibility to mimic immunosuppressive effects of tumor cell membrane PD‐L1. In this review, it is discussed whether exosomal PD‐L1 binds to antibodies and hence resistance to immunotherapy will be developed, and targeting exosome biogenesis inhibition can provide a new strategy to overcome tumor resistance to anti‐PD‐L1 therapy. Diagnostic and prognostic values of exosomal PD‐L1 in different cancer types are discussed. Multiple clinical studies conclude that the level of tumor‐derived exosomes (TEXs) as a biomarker for diagnosis could distinguish cancer patients from healthy controls. Elevated exosomal PD‐L1 levels may be predictive of advanced disease stages, cancer metastasis, lower response to anti‐PD‐1/PD‐L1 therapy, lower overall survival rates, and poor tumor prognosis. These novel findings of TEXs serve as promising therapeutic targets for early diagnosis and prevention of cancer progression. In this review, it is discussed whether exosomal PD‐L1 binds to antibodies and hence resistance to immunotherapy will be developed, and targeting exosome biogenesis inhibition can provide a new strategy to overcome tumor resistance to anti‐PD‐L1 therapy. Additionally, diagnostic and prognostic values of exosomal PD‐L1 in different cancer types are discussed.