Abstract 2152: NT-I7 increases lymphocytes and enhances chemotherapy and immunotherapy efficacy in HNSCC

Background: Lymphopenia is associated with poor outcomes and is exacerbated by conventional chemoradiation therapies in head and neck squamous cell carcinoma (HNSCC). NT-I7 (rhIL-7-hyFc, efineptakin alfa; NeoImmuneTech, Inc.), a long-acting human IL-7, has the potential to restore lymphocyte populations, modulate immune responses, and enhance anti-tumor activity. This study investigated NT-I7’s effects on lymphocyte populations and its synergy with cisplatin and immune checkpoint inhibitors (ICIs) in syngeneic, immunocompetent HNSCC mouse models. Methods: The impact of NT-I7 was studied in two syngeneic tumor models, MOC1 and MOC22. Flow cytometry and Cytometry by Time of Flight (CyTOF) analyses were used to evaluate NT-I7 effects on peripheral and intratumoral immune cells. Anti-tumor efficacy was assessed following NT-I7 treatment alone, in combination with cisplatin, or with anti-PD-1 therapy. Results: Mice bearing syngeneic MOC1 and MOC22 tumors exhibited significant lymphopenia, characterized by reductions in CD4+ and CD8+ T-cells, Tregs, NK cells, and NKT cells, resembling clinical observations in HNSCC patients. NT-I7 treatment significantly increased lymphocyte levels in both spleen and tumor, with notable induction of CD8+ T-cells and NKT cells, peaking at day 7 and day 4 post-treatment, respectively, and minimal impact on intratumoral Treg levels. NT-I7 modestly inhibited MOC1 tumor growth and potently suppressed MOC22 tumor growth. Combining NT-I7 with cisplatin significantly enhanced anti-tumor activity in MOC1 tumors, accompanied by increased numbers of peripheral and intratumoral CD4+, CD8+, and NKT cells. Furthermore, NT-I7 augmented the efficacy of anti-PD-1 therapy in MOC1 tumors, resulting in greater tumor growth inhibition compared to either treatment alone. CyTOF analysis revealed preferential expansion of CD8+ Tpex cells, a key subset of tumor-specific cells that expand in response to ICIs, highlighting NT-I7’s role in overcoming lymphopenia and potentiating anti-tumor immunity. Conclusions: NT-I7 effectively increases lymphocyte populations in HNSCC preclinical models that demonstrate tumor-associated lymphopenia, and enhances the efficacy of cisplatin and anti-PD-1 in HNSCC preclinical tumor models. Citation Format: Zhibin Cui, Jacqueline L. Yee, Hua Li, Yan Zeng, Liam Woerner, Alexandra A. Wolfarth, Sara Ferrando-Martinez, Hyunseok Kang, Jennifer R. Grandis, Matthew H. Spitzer, Daniel E. Johnson. NT-I7 increases lymphocytes and enhances chemotherapy and immunotherapy efficacy in HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2152.