(P 228) EXPLORING THE LINK BETWEEN TUMOUR INFILTRATING IMMUNE CELLS AND PATIENT OUTCOME IN SOFT TISSUE SARCOMA: A CLOSER LOOK AT MACROPHAGES

Objective: The introduction of immune-modulating therapy has revolutionised the treatment of many cancers but has only been efficient in a limited number of sarcoma patients. Sarcomas are generally regarded as non-immunogenic due to sparse immune infiltration, especially of the adaptive immune system. This is one hypothesis for why most sarcomas are unresponsive to current immune therapy. There are, however, significant differences in response to immune therapy between different subtypes of sarcoma, e.g., undifferentiated pleomorphic sarcomas (UPS) seem to respond to treatment continuously. Recently, the innate immune system has gained attention as a possible future target for therapy, especially the immune suppressive macrophages, called the M2-subtype. Here, we investigate tumour-infiltrating M2 macrophages and their influence on sarcoma patients’ survival across two subtypes of sarcoma. Our hypothesis is that a high infiltration of M2 macrophages correlate with a worse overall outcome in soft tissue sarcoma patients, which is probably also depending on subtype of sarcoma.

Methods: This study is performed on archival tissue. Blocks of formalin-fixed paraffin-embedded tissue samples were collected with corresponding haematoxylin-eosin slides, used to identify representative tumour samples. In total material from 58 patients were included for immunohistochemical analysis (IHC), 17 leiomyosarcoma (LMS) patients and 41 UPS patients. IHC was performed for M2 macrophages (CD163), B-lymphocytes (CD20), and T-lymphocytes (CD4 and CD8). IHC was evaluated semi-quantitatively, each sample being categorised into either low, moderate, or high infiltration for each protein-marker. Infiltration was further categorised spatially as either locally or globally occurring. Infiltration of M2 macrophages was evaluated in relation to patient survival (overall survival, local and distant recurrence), and sarcoma subtype.

Results: The number of patients dead: 31 (UPS n=21); and alive: 27 (UPS n=20). We found no difference in overall survival between the subtypes. The number of patients with high infiltration: 9 (UPS n=9); with moderate infiltration: 29 (UPS n=20); with low infiltration: 20 (UPS n=12).
There seems to be higher odds of dying when having a moderate infiltration compared to a low infiltration (OR=2.13 (95% CI: 0.65-6.46), p=0.25), or a high infiltration compared to low infiltration (OR=3.00 (95% CI: 0.58-12.98), p=0.25). There seems to be no relevant difference in survival between moderate and high infiltration (OR=1.41 (95% CI: 0.32-5.90), p>0.99).

Conclusion: These results indicate that there is a worse overall survival correlated with a moderate or high infiltration of M2 macrophages, which aligns well with our hypothesis. However, we also observed no difference in survival between moderate and high infiltration, and no difference in survival between the subtypes. These factors contrast with our hypothesis.
This study is the first to directly compare the presence of M2 macrophages to overall survival in sarcoma patients and may thus aid in our understanding of why sarcomas are non-responsive to current immune-modulating therapy.