One of the main mechanisms for avoiding immune response by cancer cells is mediated by inducing an immunosuppressive environment in the tumor following activation of immune checkpoints, i.e. PD-1 or CTLA-4 receptor inhibitors on T lymphocytes. Interaction inhibition between PD-1 or CTLA-4 and their ligands (PD-L1, CD80, and CD85) leads to unblocking of the T-lymphocyte function, and thus destroys cancer cells. Certain intracellular signaling pathways are also involved in the development of tumor cell immunoresistance. Immunosuppressive pathways' activation blocking may increase the immunological anti-tumor control.

Objectives To immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites. Materials and methods A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e., bleeding on probing with or without suppuration, probing depths >= 6 mm, and radiographic marginal bone loss >= 3 mm) were included. The severity of peri-implantitis was classified according to established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses. Results Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI 11.4-17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI 5.9-9.4) and 5.22% (95% CI 3.8-6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI 1-12-1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values. Conclusion The present immunohistochemical analysis suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis sites, which could possibly play a critical role in disease progression.