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Background Recurrent gliomas remain a disease of high unmet need, with limited effective therapies and progressive systemic immune exhaustion characterized by both depletion of T lymphocytes and accumulation of immunosuppressive myeloid-derived suppressor cells (MDSCs). HF1K16 is a novel immunomodulatory therapy designed to target MDSCs through a liposomal formulation of all-trans retinoic acid (ATRA), inducing differentiation and restoring immune balance. 1,2 We present updated results from the ongoing Phase I study of HF1K16 (NCT05388487) in recurrent glioma patients.Methods A total of 21 patients with recurrent or refractory glioma (9 males, 12 females) were enrolled. Eligible patients had confirmed advanced disease and prior treatment failure. HF1K16 was administered in 21-day cycles (q.o.d., days 1–14). Peripheral blood mononuclear cells (PBMCs) were collected longitudinally for multiparametric flow cytometry. In some cases, surgically resected tumor tissue after treatment of therapy was analyzed using spatial flow cytometry.Results Among 8 patients with recurrent grade 4 glioblastoma, the median overall survival (OS) was 17.7 months, with over half of patients alive beyond 12 months. In 9 evaluable patients with grade 2-3 glioma, median OS reached 26.5 months, with sustained clinical benefit during continued treatment. Longitudinal immune profiling revealed a significant reduction in circulating MDSCs during treatment, accompanied by progressive recovery of peripheral lymphocyte counts. T-cell subset analysis demonstrated that patients with higher baseline proportions of naïve T cells (Tn) derived greater benefit (PFS Tn≤20% vs. PFSTn≥20%= 64 d vs. 194 d; HR=0.086, CI95% :0.012-0.62). In a representative grade 4 glioblastoma patient treated for five cycles, spatial flow cytometry of resected tissue showed extensive T-cell infiltration within the tumor microenvironment, consistent with a transition from an immunosuppressive to an immunoreactive phenotype.Conclusions HF1K16 monotherapy demonstrates a durable clinical signal in recurrent glioma, with half of heavily pretreated patients achieving survival beyond two years. Correlative immune analyses indicate that MDSC depletion by HF1K16 restores T-cell activity and remodels the tumor microenvironment. Baseline T-cell reserve may serve as a predictive biomarker for clinical benefit. These findings support continued clinical investigation of HF1K16.Trial Registration NCT05388487References Zheng, Anjie, et al. Abstract LB205: Myeloid cell targeted immune modulation in solid tumor and brain tumor patients: An analysis of nct05388487 phase 1 study data. Cancer Research 85.8_Supplement_2 2025: LB205-LB205.Zheng, Anjie, et al. Sustained drug release from liposomes for the remodeling of systemic immune homeostasis and the tumor microenvironment. Frontiers in Immunology 13(2022):829391.Ethics Approval This study is approved by the Ethics Committee of Huashan Hospital Affiliated to Fudan University at Mar 11, 2022Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.