DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays
PD-L1 immunohistochemistry (IHC) assays are used as a companion diagnostic for immunotherapy with immune checkpoint inhibitors (ICIs). However, despite the association between PD-L1 expression and clinical benefit from ICIs, the PD-L1 IHC assay is not sufficiently accurate in predicting response to...
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MDPI AG
2024-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/13/1/56 |
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| author | Muralidharan Mani Seong Hee Choi Hyuk Nam Kwon Jeong Woo Park |
| author_facet | Muralidharan Mani Seong Hee Choi Hyuk Nam Kwon Jeong Woo Park |
| author_sort | Muralidharan Mani |
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| description | PD-L1 immunohistochemistry (IHC) assays are used as a companion diagnostic for immunotherapy with immune checkpoint inhibitors (ICIs). However, despite the association between PD-L1 expression and clinical benefit from ICIs, the PD-L1 IHC assay is not sufficiently accurate in predicting response to ICIs; some patients with high PD-L1 expression do not respond to ICIs. Recently, researchers provided insights into why some patients with high PD-L1 expression fail to respond to ICIs. They discovered that DRG2 is a critical regulator of PD-L1 endosomal trafficking in cancer cells, which is essential for the proper localization of PD-L1 on the cell surface. Although DRG2-depleted cells express high levels of PD-L1 and are PD-L1 IHC-positive, the PD-L1 sequestered in early endosomes does not respond to ICIs. Therefore, a companion diagnostic combining DRG2 expression with a PD-L1 IHC assay may improve the therapeutic response to PD-1/PD-L1 ICIs. |
| format | Article |
| id | doaj-art-f5120afe29204779ad2aff5163ef3a96 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-f5120afe29204779ad2aff5163ef3a962025-01-24T13:23:52ZengMDPI AGBiomedicines2227-90592024-12-011315610.3390/biomedicines13010056DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry AssaysMuralidharan Mani0Seong Hee Choi1Hyuk Nam Kwon2Jeong Woo Park3Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53715-1218, USARopheLBio, B102, Seoul Forest M Tower, Seoul 04778, Republic of KoreaDepartment of Biological Sciences, University of Ulsan, Ulsan 44610, Republic of KoreaDepartment of Biological Sciences, University of Ulsan, Ulsan 44610, Republic of KoreaPD-L1 immunohistochemistry (IHC) assays are used as a companion diagnostic for immunotherapy with immune checkpoint inhibitors (ICIs). However, despite the association between PD-L1 expression and clinical benefit from ICIs, the PD-L1 IHC assay is not sufficiently accurate in predicting response to ICIs; some patients with high PD-L1 expression do not respond to ICIs. Recently, researchers provided insights into why some patients with high PD-L1 expression fail to respond to ICIs. They discovered that DRG2 is a critical regulator of PD-L1 endosomal trafficking in cancer cells, which is essential for the proper localization of PD-L1 on the cell surface. Although DRG2-depleted cells express high levels of PD-L1 and are PD-L1 IHC-positive, the PD-L1 sequestered in early endosomes does not respond to ICIs. Therefore, a companion diagnostic combining DRG2 expression with a PD-L1 IHC assay may improve the therapeutic response to PD-1/PD-L1 ICIs.https://www.mdpi.com/2227-9059/13/1/56DRG2PD-L1endosomal traffickingICIpredictive efficacy |
| spellingShingle | Muralidharan Mani Seong Hee Choi Hyuk Nam Kwon Jeong Woo Park DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays Biomedicines DRG2 PD-L1 endosomal trafficking ICI predictive efficacy |
| title | DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays |
| title_full | DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays |
| title_fullStr | DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays |
| title_full_unstemmed | DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays |
| title_short | DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays |
| title_sort | drg2 as a biomarker to enhance the predictive efficacy of pd l1 immunohistochemistry assays |
| topic | DRG2 PD-L1 endosomal trafficking ICI predictive efficacy |
| url | https://www.mdpi.com/2227-9059/13/1/56 |
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