Abstract 1530: Alveolar macrophage depletion decreases lung cytokines and decreases mouse lung tumor growth.

Abstract While anti-inflammatory therapies are being evaluated in lung cancer, the role of specific immune effector cells and their products in lung carcinogenesis is unclear. Alveolar macrophage numbers increase as lung tumors progress, and subsequent changes in macrophage function are linked to increased growth factor production, accelerated tumor proliferation, enhanced angiogenesis, depressed immune response, and metastasis. However, the signaling molecules linking alveolar macrophages to advanced lung tumor growth are not well defined. To examine how macrophages drive lung tumorigenesis, clodronate-encapsulated liposomes were used to specifically deplete alveolar macrophages in mice bearing chemically-induced lung tumors. Treatment efficacy was assessed by evaluating tumor burden, multiplicity, proliferation index and histologic stage. Alveolar macrophage populations decreased to ≤ 50% of control levels during six weeks of liposomal clodronate treatment. This was associated with significantly decreased pulmonary levels of IGF-1, KC, IL-6 and CCL2. The concentrations of these cytokines strongly correlated with decreased macrophage numbers in lung lavage fluid. Tumor burden and Ki-67 index was reduced by 50% in clodronate-treated mice, corresponding with the 50% decrease in macrophage numbers and cytokine content. Therefore, macrophage depletion attenuates lung tumor proliferation in vivo, consistent with our previous observations linking macrophage IGF-1 production and lung tumor proliferation in vitro. These cytokines appear to mediate macrophage-stimulated lung tumorigenesis, and are thus potential therapeutic targets in lung cancer and chronic inflammatory lung disease. Citation Format: Jason Fritz, Meredith A. Tennis, Alvin Malkinson, Lori Dwyer-Nield. Alveolar macrophage depletion decreases lung cytokines and decreases mouse lung tumor growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1530. doi:10.1158/1538-7445.AM2013-1530