biostudies-literatureHong GKorea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of KoreaBasic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and TechnologyKorea Health Technology R&amp;D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health &amp; Welfare, Republic of KoreaChungnam National University Hospital Research Fund159-171https://www.ebi.ac.uk/biostudies/studies/S-EPMC9889409biostudies-literatureUnknown149(1)<h4>Purpose</h4>Although increased plasma growth differentiation factor-15 (GDF15) levels have been reported in patients with various cancers, the predictive role of PD-1/PD-L1 inhibitors in advanced cancers remains unknown. This study aimed to investigate GDF15 levels as a predictive marker in advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors and analyze their association with immune cell populations.<h4>Methods</h4>This study included 87 patients with advanced NSCLC receiving anti-PD-1/PD-L1 inhibitors between March 2018 and May 2020. Blood samples were obtained immediately before and months after PD-1/PD-L1 inhibitor administration.<h4>Results</h4>The objective response rate (ORR) was significantly higher in the low GDF15 than in the high GDF15 group (39.2% vs. 15.3%, P = 0.013). The median progression-free survival (PFS) was significantly longer in the low GDF15 than in the high GDF15 group (13.2 [95% CI 7.6-18.9] vs. 7.2 [95% CI 4.8-9.6] months, P = 0.048). Moreover, plasma GDF15 levels negatively correlated with PD-1⁺/CD8⁺ T cells (r = - 0.399, P = 0.003) and positively with PD-1⁺/Treg cells (r = 0.507, P < 0.001) and PD-1⁺Treg/CD4⁺ T cells (r = 0.439, P < 0.001). The ORR was significantly higher in the group with decreased GDF15 from baseline than in the increased GDF15 group (37.2% vs. 10.0%, P = 0.026). The median PFS was significantly longer in the decreased GDF15 group (14.8 [95% CI 10.4-19.2] vs. 5.9 [95% CI 2.8-9.0] months, P = 0.002). Plasma GDF15 levels were associated with PD-1⁺CD8⁺ T cells and PD-1⁺ Treg cells.<h4>Conclusion</h4>Plasma GDF15 could be a potential biomarker for predicting the efficacy and survival benefit of immunotherapy in advanced NSCLC.Journal of cancer research and clinical oncologyPlasma GDF15 levels associated with circulating immune cells predict the efficacy of PD-1/PD-L1 inhibitor treatment and prognosis in patients with advanced non-small cell lung cancer.PMC9889409HR22C1734NRF-2022R1C1C1007301NRF-2021R1C1C10111832021Chung CLee JEKang DHSun PLee SILee SEHong GKang YEPark DKim NfalsePlasma GDF15 levels associated with circulating immune cells predict the efficacy of PD-1/PD-L1 inhibitor treatment and prognosis in patients with advanced non-small cell lung cancer.<h4>Purpose</h4>Although increased plasma growth differentiation factor-15 (GDF15) levels have been reported in patients with various cancers, the predictive role of PD-1/PD-L1 inhibitors in advanced cancers remains unknown. This study aimed to investigate GDF15 levels as a predictive marker in advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors and analyze their association with immune cell populations.<h4>Methods</h4>This study included 87 patients with advanced NSCLC receiving anti-PD-1/PD-L1 inhibitors between March 2018 and May 2020. Blood samples were obtained immediately before and months after PD-1/PD-L1 inhibitor administration.<h4>Results</h4>The objective response rate (ORR) was significantly higher in the low GDF15 than in the high GDF15 group (39.2% vs. 15.3%, P = 0.013). The median progression-free survival (PFS) was significantly longer in the low GDF15 than in the high GDF15 group (13.2 [95% CI 7.6-18.9] vs. 7.2 [95% CI 4.8-9.6] months, P = 0.048). Moreover, plasma GDF15 levels negatively correlated with PD-1⁺/CD8⁺ T cells (r = - 0.399, P = 0.003) and positively with PD-1⁺/Treg cells (r = 0.507, P < 0.001) and PD-1⁺Treg/CD4⁺ T cells (r = 0.439, P < 0.001). The ORR was significantly higher in the group with decreased GDF15 from baseline than in the increased GDF15 group (37.2% vs. 10.0%, P = 0.026). The median PFS was significantly longer in the decreased GDF15 group (14.8 [95% CI 10.4-19.2] vs. 5.9 [95% CI 2.8-9.0] months, P = 0.002). Plasma GDF15 levels were associated with PD-1⁺CD8⁺ T cells and PD-1⁺ Treg cells.<h4>Conclusion</h4>Plasma GDF15 could be a potential biomarker for predicting the efficacy and survival benefit of immunotherapy in advanced NSCLC.2023-01-01T00:00:00Z2023 Jan2025-04-21T22:49:48.282Z2025-04-05T18:52:42.686ZS-EPMC98894093647277010.1007/s00432-022-04500-5