Soluble lymphocyte activation gene-3 (sLAG3) and CD4/CD8 ratio dynamics as predictive biomarkers in patients undergoing immune checkpoint blockade for solid malignancies

TY - JOUR

T1 - Soluble lymphocyte activation gene-3 (sLAG3) and CD4/CD8 ratio dynamics as predictive biomarkers in patients undergoing immune checkpoint blockade for solid malignancies

AU - Gorgulho, Joao

AU - Roderburg, Christoph

AU - Beier, Fabian

AU - Bokemeyer, Carsten

AU - Brümmendorf, Tim H

AU - Loosen, Sven H

AU - Luedde, Tom

N1 - © 2024. The Author(s).

PY - 2024/4

Y1 - 2024/4

N2 - BACKGROUND: The search for biomarkers to identify suitable candidates for immune checkpoint inhibitor (ICI) therapy remains ongoing. We evaluate how soluble levels of the next generation immune checkpoint Lymphocyte Activation Gene-3 (sLAG-3) and its association with circulating T lymphocyte subsets could pose as a novel biomarker to predict outcome to ICI therapy.METHODS: Circulating levels of sLAG3 were analyzed using multiplex immunoassay in n = 84 patients undergoing ICI therapy for advanced solid cancer, accompanied by flow cytometry analyses of peripheral blood mononuclear cells (PBMCs).RESULTS: Uni- and multivariate analysis shows that patients with higher sLAG3 concentrations before ICI therapy had a significantly impaired progression-free (PFS) and overall survival (OS) (HRPFS: 1.005 [95%CI: 1.000-1.009], p = 0.039; HROS: 1.006 [95%CI: 1.001-1.011], p = 0.015). The CD4/CD8 cell ratio and its dynamics during therapy were strong predictors of PFS and OS with patients with a decreasing ratio between baseline and after 1-2 cycles having an improved median OS compared to patients with increasing values (p = 0.012, HR: 3.32). An immunological score combining sLAG3 and the CD4/CD8 ratio showed the highest predictive potential (HROS: 10.3).CONCLUSION: Pending prospective validation, sLAG3 and correlating circulating T-cell subsets can be used as a non-invasive predictive marker to predict outcome to ICI therapy to help identifying ideal ICI candidates in the future.

AB - BACKGROUND: The search for biomarkers to identify suitable candidates for immune checkpoint inhibitor (ICI) therapy remains ongoing. We evaluate how soluble levels of the next generation immune checkpoint Lymphocyte Activation Gene-3 (sLAG-3) and its association with circulating T lymphocyte subsets could pose as a novel biomarker to predict outcome to ICI therapy.METHODS: Circulating levels of sLAG3 were analyzed using multiplex immunoassay in n = 84 patients undergoing ICI therapy for advanced solid cancer, accompanied by flow cytometry analyses of peripheral blood mononuclear cells (PBMCs).RESULTS: Uni- and multivariate analysis shows that patients with higher sLAG3 concentrations before ICI therapy had a significantly impaired progression-free (PFS) and overall survival (OS) (HRPFS: 1.005 [95%CI: 1.000-1.009], p = 0.039; HROS: 1.006 [95%CI: 1.001-1.011], p = 0.015). The CD4/CD8 cell ratio and its dynamics during therapy were strong predictors of PFS and OS with patients with a decreasing ratio between baseline and after 1-2 cycles having an improved median OS compared to patients with increasing values (p = 0.012, HR: 3.32). An immunological score combining sLAG3 and the CD4/CD8 ratio showed the highest predictive potential (HROS: 10.3).CONCLUSION: Pending prospective validation, sLAG3 and correlating circulating T-cell subsets can be used as a non-invasive predictive marker to predict outcome to ICI therapy to help identifying ideal ICI candidates in the future.

U2 - 10.1038/s41416-023-02558-7

DO - 10.1038/s41416-023-02558-7

M3 - SCORING: Journal article

C2 - 38233492

VL - 130

SP - 1013

EP - 1022

JO - BRIT J CANCER

JF - BRIT J CANCER

SN - 0007-0920

IS - 6

ER -