Abstract
Abstract Numerous studies indicate that certain tumor-infiltrating macrophage subsets can support neoplastic growth. Recent reports showed that spleen can serve as an important reservoir for macrophages and neutrophils that replicate in situ, then migrate to support tumor growth. Eribulin mesylate (Halaven®) is a microtubule-dynamics inhibitor approved for third line clinical use in patients with heavily pretreated metastatic breast cancer based upon statistically significant increase in median overall survival (OS) compared to treatment of physician's choice. In an effort to understand whether eribulin has additional effects beyond its anti-mitotic activity, the current study addressed the effects of eribulin mesylate on immune cells. Using the subcutaneous syngeneic murine tumor model Lewis lung carcinoma (LLC), we found that the tumor shrinking effect of eribulin correlated with increased extramedullary hematopoiesis observed in the spleens of treated mice. Eribulin was also found to inhibit the proliferation of M2 tumor-associated macrophages (TAMs) in the spleens of LLC-bearing mice. Early effects of eribulin were studied using the CT-26 colon tumor isograft model and included increased differentiation and death of CD4+ and CD8+ effector T cells. Furthermore, eribulin caused increased CD25 expression on CD4+ Foxp3- T cells but not on CD4+ Foxp3+ T regulatory cells. Finally, frequencies of exhausted CD8+ T cells were reduced following eribulin treatment. Taken together, these results suggest that eribulin-mediated modulation of immune homeostasis especially in the spleen, may contribute to its anti-tumor effect. Citation Format: Diana I. Albu, Namita Kumar, Galina Kusnetzov, Shanqin Xu, Bruce Littlefield, Mary Woodall-Jappe. Eribulin mesylate alters immune homeostasis in mice bearing syngeneic tumors. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B90.
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