Abstract 3970: Tumor-associated macrophage, angiogenesis and lymphangiogenesis predicts prognosis in patients with non-small cell lung cancer

Abstract

Abstract Background: The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcome. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME, and are generally characterized as M2-like macrophages. TAMs are believed to contribute to tumor progression, but the mechanism behind this remains unclear. We aimed to investigate the clinical value, angiogenic and lymphangiogenic significance of TAMs in non-small cell lung cancer (NSCLC). Methods: We assessed CD68, CD163, VEGF-A, and VEGF-C expression in 349 patients with NSCLC by combined immunohistochemistry and digital image analysis. Subsequently, the potential association between M2 TAMs and angiogenetic VEGF-A and/or lymphangiogenetic VEGF-C was evaluated for its prognostic value. Furthermore, the effects of M2 TAMs on angiogenesis and lymphangiogenesis were explored in vitro co-culture system. Results: Elevated M2 (CD163+/CD68+) ratio was significantly associated with poor overall survival (p=0.023). Dual high expression of M2 ratio and VEGF-C was correlated with worse overall survival (p=0.033). Furthermore, CD68 and CD163 expression are positively associated with VEGF-A and/or VEGF-C expression. Multivariate analysis revealed that M2 ratio was an independent predictor of poor survival [HR (95% CI) = 1.53 (1.01-2.33), p=0.046]. Combined M2+/VEGF-C+ expression was also an independent predictor of poor survival [HR (95% CI) = 2.01 (1.28-3.16), p=0.003]. Notably, we confirmed that M2 macrophages enhanced the protein and mRNA expression of both VEGF-A and VEGF-C significantly, while M1 macrophages induced only mRNA expression of VEGF-A significantly in A549 cells. Conclusions: This study suggests that TAMs are significantly associated with angiogenesis or lymphangiogenesis in the progression of NSCLC. Furthermore, elevated M2 ratio and combined M2 and VEGF-C high expression are strong indicators of poor prognosis in patients with NSCLC. Citation Format: Ilseon Hwang, Keun Uk Park, Eun Hee Jung, Hun-Mo Ryoo, Kris Ylaya, Joon-Yong Chung, Stephen M. Hewitt. Tumor-associated macrophage, angiogenesis and lymphangiogenesis predicts prognosis in patients with non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3970.