PPARD and head and neck squamous cell carcinoma: However, not all malignancies display a uniform shift towards M2 polarization. For instance, exosomes derived from Human Papillomavirus (HPV)-positive HNSCC induce M1 polarization of macrophages, rather than M2 [50]. Specifically, exosomal miR-9, which is enriched in HPV+ HNSCC, was shown to promote M1 macrophage polarization by downregulating PPARδ, thereby increasing tumor radiosensitivity and improving prognosis [51].