Background: Baseline Neutrophil-to-Lymphocyte (L) ratio (NLR), Platelet-to-L ratio (PLR), and L-to-Monocyte ratio (LMR) are biomarkers that can predict anticancer outcomes. Plin, a novel small molecule immune-enhancing agent, exerts anticancer activity by GEF-H1-dependent activation of dendritic cells, and hence T-cells. We evaluated the correlation of Plin’s anticancer effects with NLR, PLR, LMR immune suppressive (IS) signature. We correlated baseline NLR, PLR, and LMR (broken down in quartiles [Q]) with overall survival (OS) in NSCLC pts from the DUBLIN-3 trial, which had met the primary OS endpoint in favor of Plin/Doc vs Doc alone (Han ESMO 2021). Methods: DUBLIN-3 (NCT02504489) was a global Phase 3 study in 2^nd/3^rd line EGFR-wild type, stage IIIB/IV NSCLC pts (N = 559) randomized 1:1 to Plin/Doc or Doc alone. Doc (75 mg/m² on D1) and Plin (30 mg/m² on D1/D8) were given by IV infusions. Baseline (i.e., prior to dexamethasone premedication, Doc and Plin) blood draws were taken from each pt within 28 days prior to any study medication given to obtain baseline NLR, PLR, and LMR. The survival duration of each pt was obtained. NLR, PLR, and LMR values for Plin/Doc and Doc were divided into Qs, and the corresponding median OS for each Q was calculated. Only 2^nd line pts were included in this analysis to avoid confounding with multiple lines. Results: Increasing Qs of baseline NLR and PLR (thus with increasing IS signature) were associated with decreasing median OS for both Plin/Doc and Doc. Increasing Qs for LMR (thus with decreasing IS signature) were associated with increasing median OS in both Plin/Doc and Doc. Median OS in each Q was consistently higher with Plin/Doc vs Doc alone, except for Qs with an IS signature. With baseline NLR ≤3.6, PLR≤194, or LMR≥5.9, thus avoiding an IS signature, median OS was on average 2.5 Mo (range 0.6-4.5 Mo) longer with Plin/Doc vs Doc alone. For each of the Qs in the table, the n = 52 ± 2 pts. Conclusions: Baseline IS biomarkers were predictive of median OS with both Plin/Doc and Doc alone. Baseline NLR, PLR, and LMR, at cut-off levels to avoid IS levels, could serve as prognostic markers to identify likely responders to the immune-enhancing agent Plin in combination with Doc in NSCLC. Clinical trial information: NCT02504489.