title: Low dose photodynamic-therapy induce immune escape of tumor cells in a HIF-1α dependent manner through PI3K/Akt pathway.
abstract: As a regulatory approved antitumor therapy, photodynamic therapy (PDT) shows poor effect in clinical application. The current study aimed at investigating the mechanism through which low-dose PDT affects the immune escape ability of Lewis lung carcinoma (LLC) cells. Our data show that low-dose PDT could increase HIF-1α expression through the activation of the PI3K/Akt pathway. Our results also show that low-dose PDT treatment can increase tumor growth rate in C57BL/6 mice, reducing the survival of tumor-bearing mice. Furthermore, low-dose PDT could increase regulatory T cells (Tregs) number, decrease the cytotoxic T lymphocytes (CTLs) number, and induce CTLs apoptosis in co-culture system in vitro. The immunosuppression caused by low dose PDT could be partially abolished by knocking down the hypoxia-inducible factor 1α (HIF-1α) and blocking the phosphatidylinositol 3-kinase (PI3K). Our results suggest that low dose PDT may enhance immune escape of LLC cells in a HIF-1α dependent manner through PI3K/Akt pathway. The present study thus offers a new insight on elucidating the mechanism whereby low dose PDT induces tumor progression and therapy-resistance, providing a novel approach for cancer immunotherapy.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Che
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Kang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address: wanjun622@126.com.
authors.forename: RenQuan
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051058:Oncogene Protein v-akt / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects*; D010778:Photochemotherapy / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D019139:Tumor Escape / Q000528:radiation effects*
chemical_list: D016207:Cytokines; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: HIF-1α; Immune escape; Lewis lung carcinoma; PI3K/Akt pathway; Photodynamic therapy