Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies
Lymphocyte-activation gene-3 (LAG-3), an immune checkpoint receptor, negatively regulates T-cell function and facilitates immune escape of tumors. Dual inhibition of LAG-3 and programmed cell death receptor-1 (PD-1) significantly improved progression-free survival (PFS) in metastatic melanoma patien...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261248 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850035429416370176 |
|---|---|
| author | Tuba N. Gide Elizabeth C. Paver Zarwa Yaseen Nigel Maher Nurudeen Adegoke Alexander M. Menzies Ines Pires da Silva James S. Wilmott Georgina V. Long Richard A. Scolyer |
| author_facet | Tuba N. Gide Elizabeth C. Paver Zarwa Yaseen Nigel Maher Nurudeen Adegoke Alexander M. Menzies Ines Pires da Silva James S. Wilmott Georgina V. Long Richard A. Scolyer |
| author_sort | Tuba N. Gide |
| collection | DOAJ |
| description | Lymphocyte-activation gene-3 (LAG-3), an immune checkpoint receptor, negatively regulates T-cell function and facilitates immune escape of tumors. Dual inhibition of LAG-3 and programmed cell death receptor-1 (PD-1) significantly improved progression-free survival (PFS) in metastatic melanoma patients compared to anti-PD-1 therapy alone. Investigating the utility of LAG-3 expression as a biomarker of response to anti-LAG-3 + anti-PD-1 immunotherapy is of great clinical relevance. This study sought to evaluate the association between baseline LAG-3 expression and clinical outcomes following anti-LAG-3 and anti-PD-1-based immunotherapy in metastatic melanoma. LAG-3 immunohistochemistry (clone D2G4O) was performed on pre-treatment formalin-fixed, paraffin-embedded metastatic melanoma specimens from 53 patients treated with combination anti-LAG-3 + anti-PD-1-based therapies. Eleven patients had received prior anti-PD-1-based treatment. Patients were categorized as responders (complete/partial response; n = 36) or non-responders (stable/progressive disease; n = 17) based on the Response Evaluation Criteria in Solid Tumours (RECIST). Tumor-infiltrating lymphocytes (TILs) were scored on hematoxylin and eosin-stained sections. LAG-3 expression was observed in 81% of patients, with staining in TILs and dendritic cells. Responders displayed significantly higher proportions of LAG-3+ cells compared to non-responders (P = .0210). LAG-3 expression positively correlated with TIL score (P < .01). There were no significant differences in LAG-3 expression between different sites of metastases (P > .05). Patients with ≥ 1% LAG-3+ cells in their tumors had significantly longer PFS compared to patients with < 1% LAG-3 expression (P = .0037). No significant difference was observed in overall survival between the two groups (P = .1417). Therefore, the assessment of LAG-3 expression via IHC warrants further evaluation to determine its role as a predictive marker of response and survival in metastatic melanoma. |
| format | Article |
| id | doaj-art-de51474a80d24f65bee9d63be6c7447f |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-de51474a80d24f65bee9d63be6c7447f2025-08-20T02:57:29ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2261248Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapiesTuba N. Gide0Elizabeth C. Paver1Zarwa Yaseen2Nigel Maher3Nurudeen Adegoke4Alexander M. Menzies5Ines Pires da Silva6James S. Wilmott7Georgina V. Long8Richard A. Scolyer9Melanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaMelanoma Institute Australia, The University of Sydney, Sydney, AustraliaLymphocyte-activation gene-3 (LAG-3), an immune checkpoint receptor, negatively regulates T-cell function and facilitates immune escape of tumors. Dual inhibition of LAG-3 and programmed cell death receptor-1 (PD-1) significantly improved progression-free survival (PFS) in metastatic melanoma patients compared to anti-PD-1 therapy alone. Investigating the utility of LAG-3 expression as a biomarker of response to anti-LAG-3 + anti-PD-1 immunotherapy is of great clinical relevance. This study sought to evaluate the association between baseline LAG-3 expression and clinical outcomes following anti-LAG-3 and anti-PD-1-based immunotherapy in metastatic melanoma. LAG-3 immunohistochemistry (clone D2G4O) was performed on pre-treatment formalin-fixed, paraffin-embedded metastatic melanoma specimens from 53 patients treated with combination anti-LAG-3 + anti-PD-1-based therapies. Eleven patients had received prior anti-PD-1-based treatment. Patients were categorized as responders (complete/partial response; n = 36) or non-responders (stable/progressive disease; n = 17) based on the Response Evaluation Criteria in Solid Tumours (RECIST). Tumor-infiltrating lymphocytes (TILs) were scored on hematoxylin and eosin-stained sections. LAG-3 expression was observed in 81% of patients, with staining in TILs and dendritic cells. Responders displayed significantly higher proportions of LAG-3+ cells compared to non-responders (P = .0210). LAG-3 expression positively correlated with TIL score (P < .01). There were no significant differences in LAG-3 expression between different sites of metastases (P > .05). Patients with ≥ 1% LAG-3+ cells in their tumors had significantly longer PFS compared to patients with < 1% LAG-3 expression (P = .0037). No significant difference was observed in overall survival between the two groups (P = .1417). Therefore, the assessment of LAG-3 expression via IHC warrants further evaluation to determine its role as a predictive marker of response and survival in metastatic melanoma.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261248LAG-3biomarkerimmune checkpoint inhibitorsimmunotherapymelanoma |
| spellingShingle | Tuba N. Gide Elizabeth C. Paver Zarwa Yaseen Nigel Maher Nurudeen Adegoke Alexander M. Menzies Ines Pires da Silva James S. Wilmott Georgina V. Long Richard A. Scolyer Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies OncoImmunology LAG-3 biomarker immune checkpoint inhibitors immunotherapy melanoma |
| title | Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies |
| title_full | Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies |
| title_fullStr | Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies |
| title_full_unstemmed | Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies |
| title_short | Lag-3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti-lag-3 + anti-PD-1-based immunotherapies |
| title_sort | lag 3 expression and clinical outcomes in metastatic melanoma patients treated with combination anti lag 3 anti pd 1 based immunotherapies |
| topic | LAG-3 biomarker immune checkpoint inhibitors immunotherapy melanoma |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2261248 |
| work_keys_str_mv | AT tubangide lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT elizabethcpaver lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT zarwayaseen lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT nigelmaher lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT nurudeenadegoke lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT alexandermmenzies lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT inespiresdasilva lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT jamesswilmott lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT georginavlong lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies AT richardascolyer lag3expressionandclinicaloutcomesinmetastaticmelanomapatientstreatedwithcombinationantilag3antipd1basedimmunotherapies |