Macrophage and lymphocyte infiltration is associated with volumetric tumor size but not with volumetric growth in the tübingen schwannoma cohort

Abstract

Vestibular schwannomas are benign tumors arising from the 8th cranial nerve. With microsurgical resection or radiation therapy, most patients can be cured. However, recurrent tumors are difficult to treat, and there are no other established treatment options besides local treatment. Growing evidence of the oncogenic role of inflammatory processes in schwannomas gives hope to find treatable targets for innovative therapeutic strategies. To further define inflammatory cell infiltration in this tumor type, we analyzed tumor tissue for macrophage and lymphocyte infiltrates and compared it with volumetric tumor size and growth. Increased inflammatory cell infiltration was found to be associated with larger tumor size but not with volumetric growth. Most patients with vestibular schwannomas can be cured with microsurgical resection, or tumor growth can be stabilized by radiotherapy in certain cases. Recurrence is rare but usually difficult to treat. Treatment alternatives to local therapies are not established. There is growing evidence of the role of inflammatory processes in schwannomas, which may be exploitable by targeted innovative therapies. To further define the impact of inflammation with tumor growth in vestibular schwannoma, we performed immunohistochemical analyses of CD3, CD8, CD68 and CD163 to assess lymphocyte and macrophage infiltration in 923 tumor tissue samples of surgically resected vestibular schwannomas. An inflammatory score was compared with tumor size and volumetric growth. We observed a significantly larger preoperative tumor size with increased expression rates of CD3, CD8, CD68 and CD163 (p < 0.0001, p < 0.0001, p = 0.0015 and p < 0.0001, respectively), but no differences in percentual volumetric tumor growth. When all four markers were combined as an inflammatory score, tumors with high inflammatory infiltration showed slower percentual growth in a multivariate analysis, including MIB1 expression (p = 0.0249). We conclude that inflammatory cell infiltration increases with larger tumor size but is associated with slower percentual volumetric tumor growth.