The increased expression of complement factors (C4A, C4B, C5, and C1R/S, among others) in PFD-sEVs between diagnostic samples and controls or recurrence samples could be related to previous findings suggesting that extracellular activation of this cascade by TAMs represents an innate mechanism of immunosuppression that maintains a chronic inflammatory status promoting tumor progression (44, 45). Here, C5 is linked to neoplasm.