Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy
This manuscript assesses the critical role of exosomal PD-L1 (ExoPD-L1) in immune suppression, tumor progression, and resistance to therapy. ExoPD-L1 has been identified as a key mediator of tumor immune evasion, contributing to systemic immunosuppression beyond the tumor microenvironment (TME) due...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/47/7/525 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850078300475490304 |
|---|---|
| author | Laura Denisa Dragu Mihaela Chivu-Economescu Ioana Madalina Pitica Lilia Matei Coralia Bleotu Carmen Cristina Diaconu Laura Georgiana Necula |
| author_facet | Laura Denisa Dragu Mihaela Chivu-Economescu Ioana Madalina Pitica Lilia Matei Coralia Bleotu Carmen Cristina Diaconu Laura Georgiana Necula |
| author_sort | Laura Denisa Dragu |
| collection | DOAJ |
| description | This manuscript assesses the critical role of exosomal PD-L1 (ExoPD-L1) in immune suppression, tumor progression, and resistance to therapy. ExoPD-L1 has been identified as a key mediator of tumor immune evasion, contributing to systemic immunosuppression beyond the tumor microenvironment (TME) due to its capacity to travel to distant anatomical sites. In this context, the review aims to elaborate on the mechanisms by which exosomal PD-L1 interacts with T cell receptors and modulates both the tumor microenvironment and immune responses, impacting patient outcomes. We further explore emerging therapeutic strategies that target ExoPD-L1 to enhance the effectiveness of immunotherapy. Blocking ExoPD-L1 offers a novel approach to counteracting immune escape in cancer. Promising strategies include inhibiting exosome biogenesis with GW4869 or Rab inhibitors, neutralizing ExoPD-L1 with targeted antibodies, and silencing PD-L1 expression through RNA interference (RNAi) or CRISPR-based methods. While each approach presents certain limitations, their integration into combination therapies holds significant potential to improve the efficacy of immune checkpoint inhibitors. Future research should focus on optimizing these strategies for clinical application, with particular attention to improving delivery specificity and minimizing off-target effects. |
| format | Article |
| id | doaj-art-eea83d933eea4821bed76c2075edd3b0 |
| institution | DOAJ |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj-art-eea83d933eea4821bed76c2075edd3b02025-08-20T02:45:34ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-07-0147752510.3390/cimb47070525Targeting Exosomal PD-L1 as a New Frontier in Cancer ImmunotherapyLaura Denisa Dragu0Mihaela Chivu-Economescu1Ioana Madalina Pitica2Lilia Matei3Coralia Bleotu4Carmen Cristina Diaconu5Laura Georgiana Necula6Stefan S. Nicolau Institute of Virology, 030304 Bucharest, RomaniaStefan S. Nicolau Institute of Virology, 030304 Bucharest, RomaniaStefan S. Nicolau Institute of Virology, 030304 Bucharest, RomaniaStefan S. Nicolau Institute of Virology, 030304 Bucharest, RomaniaStefan S. Nicolau Institute of Virology, 030304 Bucharest, RomaniaStefan S. Nicolau Institute of Virology, 030304 Bucharest, RomaniaStefan S. Nicolau Institute of Virology, 030304 Bucharest, RomaniaThis manuscript assesses the critical role of exosomal PD-L1 (ExoPD-L1) in immune suppression, tumor progression, and resistance to therapy. ExoPD-L1 has been identified as a key mediator of tumor immune evasion, contributing to systemic immunosuppression beyond the tumor microenvironment (TME) due to its capacity to travel to distant anatomical sites. In this context, the review aims to elaborate on the mechanisms by which exosomal PD-L1 interacts with T cell receptors and modulates both the tumor microenvironment and immune responses, impacting patient outcomes. We further explore emerging therapeutic strategies that target ExoPD-L1 to enhance the effectiveness of immunotherapy. Blocking ExoPD-L1 offers a novel approach to counteracting immune escape in cancer. Promising strategies include inhibiting exosome biogenesis with GW4869 or Rab inhibitors, neutralizing ExoPD-L1 with targeted antibodies, and silencing PD-L1 expression through RNA interference (RNAi) or CRISPR-based methods. While each approach presents certain limitations, their integration into combination therapies holds significant potential to improve the efficacy of immune checkpoint inhibitors. Future research should focus on optimizing these strategies for clinical application, with particular attention to improving delivery specificity and minimizing off-target effects.https://www.mdpi.com/1467-3045/47/7/525ExoPD-L1exosomeimmune evasioncancer immunotherapytherapy resistance |
| spellingShingle | Laura Denisa Dragu Mihaela Chivu-Economescu Ioana Madalina Pitica Lilia Matei Coralia Bleotu Carmen Cristina Diaconu Laura Georgiana Necula Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy Current Issues in Molecular Biology ExoPD-L1 exosome immune evasion cancer immunotherapy therapy resistance |
| title | Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy |
| title_full | Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy |
| title_fullStr | Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy |
| title_full_unstemmed | Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy |
| title_short | Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy |
| title_sort | targeting exosomal pd l1 as a new frontier in cancer immunotherapy |
| topic | ExoPD-L1 exosome immune evasion cancer immunotherapy therapy resistance |
| url | https://www.mdpi.com/1467-3045/47/7/525 |
| work_keys_str_mv | AT lauradenisadragu targetingexosomalpdl1asanewfrontierincancerimmunotherapy AT mihaelachivueconomescu targetingexosomalpdl1asanewfrontierincancerimmunotherapy AT ioanamadalinapitica targetingexosomalpdl1asanewfrontierincancerimmunotherapy AT liliamatei targetingexosomalpdl1asanewfrontierincancerimmunotherapy AT coraliableotu targetingexosomalpdl1asanewfrontierincancerimmunotherapy AT carmencristinadiaconu targetingexosomalpdl1asanewfrontierincancerimmunotherapy AT laurageorgiananecula targetingexosomalpdl1asanewfrontierincancerimmunotherapy |