Objectives In patients with malignant pleural mesothelioma (MPM), local tumor outgrowth (LTO) after invasive procedures is a well-known complication. Currently, no biomarker is available to predict the occurrence of LTO. This study aims to investigate whether the tumor macrophage infiltration and phenotype of and/or the infiltration of CD8 + T-cells predicts LTO. Materials and methods Ten mesothelioma patients who developed LTO were clinically and pathologically matched with 10 non-LTO mesothelioma patients. Immunohistochemistry was performed on diagnostic biopsies to determine the total TAM (CD68), the M2 TAM (CD163) and CD8 + T-cell count (CD8). Results The mean M2/total TAM ratio differed between the two groups: 0.90 ± 0.09 in the LTO group versus 0.63 ± 0.09 in patients without LTO ( p < 0.001). In addition, the mean CD8 + T-cell count was significantly different between the two groups: 30 per 0.025 cm 2 (range 2–60) in the LTO group and 140 per 0.025 cm 2 (range 23–314) in the patients without LTO ( p < 0.01). Conclusion This study shows that patients who develop LTO after a local intervention have a higher M2/total TAM ratio and lower CD8 + cell count at diagnosis compared to patients who did not develop this outgrowth. We propose that the M2/total TAM ratio and the CD8 + T-cell amount are potential tools to predict which MPM patients are prone to develop LTO. [ABSTRACT FROM AUTHOR]