title: Immunological significance of the accumulation of autophagy components in oral squamous cell carcinoma.
abstract: The immunological significance of autophagy in the tumor microenvironment remains unclear. To explore the relationship between autophagy and anti-tumor immune responses, we investigated the expression of autophagy-related proteins and infiltration of immune cells using immunohistochemistry (IHC). The expression of three representative autophagy components, LC3, Beclin-1 and p62/SQSTM1, as well as the number of dendritic cells (DC), T cells and NK cells were examined by IHC in 74 patients with oral squamous cell carcinoma (OSCC). The relationship between the expression of autophagy-associated molecules and various clinicopathological parameters was also evaluated. The expression of both LC3 and p62/SQSTM1 in the peripheral site significantly correlated with an increase in the infiltration of T cells. Furthermore, the expression of p62/SQSTM1 and Beclin-1 correlated with that of HLA class I and class II in tumor cells, respectively. In addition, several unfavorable clinicopathological parameters correlated with an increase in the expression of LC3 in the peripheral site. The correlation observed between LC3 or p62/SQSTM1 and the infiltration of T cells suggests that autophagy may actively mobilize immune cells toward the cancer bed. Meanwhile, the three autophagy-associated proteins examined were linked to malignant potential and an unfavorable prognosis.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sakakura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyoda
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Oyama
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chikamatsu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D000071456:Sequestosome-1 Protein; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein
keywords: Autophagy; LC3; immune infiltrates; oral squamous cell carcinoma; p62/SQSTM1