Abstract 2828: Paclitaxel induces colocalization of CXCL9+ tumor-associated macrophages and CD8+ T cells to potentiate antitumor immunity in head and neck squamous cell carcinoma

Abstract Background: Paclitaxel is a key chemotherapeutic agent for head and neck squamous cell carcinoma (HNSCC). Recent studies have suggested the role of paclitaxel in immune responses, particularly relevant to tumor-associated macrophages (TAMs). This study explores the immunomodulatory role of paclitaxel in the tumor microenvironment (TME), focusing on its interaction with TAMs in HNSCC. Methods: In vitro and in vivo studies were conducted on murine samples and human samples from our tertiary referral center. The in vitro experiment involved murine bone marrow-derived macrophages (BMDMs) to evaluate phagocytic functions and the expression of MHC-related genes and proteins. Our in vivo study aimed to discriminate the spatial characteristics of SPP1+/CXCL9+ TAMs and their interaction with CD8+ T cells, especially under exposure to paclitaxel, using mouse oral carcinoma (MOC) and HNSCC samples. Results: Paclitaxel enhanced macrophage phagocytosis and upregulated antigen processing genes. In the murine HNSCC model, paclitaxel combined with anti-PD-1 significantly suppressed tumor growth, whereas either treatment alone was ineffective. This was associated with the redistribution of CXCL9+ TAMs into the tumor core. Consistently, human HNSCC samples demonstrated that paclitaxel-based neoadjuvant chemotherapy (NAC) was linked to improved survival and increased infiltration of CXCL9+ TAMs and CD8+ T cells into the tumor core, indicating a shift from an "immune-excluded" to an "inflamed" microenvironment. Conclusion: Paclitaxel upregulates the phagocytic and antigen-presenting function of TAMs while spatially redistributing them toward the tumor core and subsequently inducing CD8+ T cell infiltration. Such features suggest that Paclitaxel may reprogram an immune-deserted TME to an anti-tumoral condition, ultimately contributing to immunotherapy responsiveness. Citation Format: Minsu Kwon, Jeong Heon Kim, Jisu Hong, Seo-Won Choi, Jung Min Kim, Hyo Jung Cho, Myungchan Park, JI-HYUN SEO, Jung Je Park. Paclitaxel induces colocalization of CXCL9+ tumor-associated macrophages and CD8+ T cells to potentiate antitumor immunity in head and neck squamous cell carcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2828.