Role of hyperthermia in overcoming HPV‑mediated MHC‑Ⅰ downregulation and promoting immune surveillance.

Immune‑regulatory dysfunction caused by human papillomavirus (HPV) infection can lead to severe condyloma acuminate (CA), and the treatment is challenged by obstinacy and recurrence. Hyperthermia treatment stimulates the immune response by raising the body temperature locally to fight pathogens. Hyperthermia treatment possesses advantages of low recurrence rate and good efficacy in curing viral warts. However, the exact modulatory mechanism of hyperthermia treatment on immune response remains to be addressed. HPV 16 pseudovirus (HPV.PSV)‑infected HaCaT cells were established to mimic clinical HPV infection. Flow cytometry showed higher major histocompatibility complex class I (MHC‑I) expression in HPV.PSV infected cells. HPV.PSV‑infected cells, CaSki cells and CA tissue demonstrated upregulated MHC‑Ⅰ expression following 44˚C water bath incubation, as detected by flow cytometry and IHC. 4D‑FastDIA quantitative proteomics was used to analyze differential protein expression in CaSki cells following 37‑ or 44˚C incubation. High mobility group box (HMGB)1 was upregulated following 44˚C incubation, as shown by ELISA and western blotting. By applying HMGB1 knockdown cell lines established by small interfering RNA, the present study demonstrated HMGB1 was essential to MHC‑Ⅰ expression, which was detected by flow cytometry and the recombinant HMGB1 protein addition test. Western blotting and ELISA demonstrated that hyperthermia increased heat shock protein family A member 6 (HSPA6) expression and JNK phosphorylation, which resulted in greater secretion of HMGB1. Hyperthermia treatment facilitated HSPA6‑modulated JNK phosphorylation, which lead to HMGB1 secretion and enhanced the expression of MHC‑Ⅰ in HPV‑infected epithelial cells, as well as strengthened the host immune regulation and recognition.