EXPLORING IMMUNE CHECKPOINT EXPRESSION IN PERIPROSTHETIC JOINT INFECTION: VISTA AND TIM-3

Aim Cancer research has demonstrated that immune checkpoints have a central role in mediating immunosuppressive signalling within tumors. Immune checkpoint inhibitors, designed to block these signals, can enhance immune responses to eliminate cancer cells. Emerging evidence suggests that bacteria, similar to cancer cells, can upregulate immune checkpoints to escape immunosurveillance. Here, we explore if immune checkpoints are also upregulated in intraoperative tissue samples from periprosthetic joint infection (PJI). Method Paraffin-embedded periprosthetic membrane tissue from 35 patients (mean age: 69 years) undergoing revision surgery of a hip or knee joint was obtained and classified as infected (n=17) or aseptic (n=18) according to EBJIS diagnostic criteria. Tissue sections were stained with immunohistochemical protocols towards the immune checkpoints VISTA and TIM-3. A pixel classifier algorithm was trained to quantify positive immune checkpoint staining in digitally scanned tissue sections using the bioimage analysis software QuPath (Figure 1). Results The percentage of global VISTA staining was significantly increased in infected (mean: 1.4%, range: 0.05-5.7%) compared to aseptic revisions (mean: 0.4%, range: 0.008-1.9%), while there was no difference in TIM-3 staining. VISTA primarily stained neutrophils and lymphocytes, while TIM-3 broadly stained cells such as lymphocytes, macrophages, giant cells and fibroblasts. The percentage of VISTA and TIM-3 staining showed a significant correlation with joint type, with higher staining observed in tissue from knee compared to hip joints (r = 0.34-0.51). Conclusions Increased expression of VISTA suggests that local immunosuppression is present in PJI. Therefore, it seems relevant to investigate immune checkpoints as immunotherapeutic targets for PJI. The observed heterogeneity in immune checkpoint expression among patients may reflect individual variations in immune responses during PJI. Further research on different immune checkpoints with distinct functional properties across larger patient populations is needed to understand their potential as therapeutic targets in PJI settings. Acknowledgements Funding: Novo Nordisk Foundation and Gigtforeningen For any figures or tables, please contact the authors directly.