Immunological significance of the accumulation of autophagy components in oral squamous cell carcinoma

• Published in: Cancer science 2015-01, Vol.106 (1), p.1-8
• Main Authors: Sakakura, Koichi, Takahashi, Hideyuki, Kaira, Kyoichi, Toyoda, Minoru, Oyama, Tetsunari, Chikamatsu, Kazuaki
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Adult; Aged; Aged, 80 and over; Apoptosis Regulatory Proteins - metabolism; Autophagy; Beclin-1; Cancer; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; Chemotherapy; Dendritic cells; Female; Histocompatibility antigen HLA; Humans; immune infiltrates; Immunohistochemistry; Immunology; Kaplan-Meier Estimate; Killer Cells, Natural - immunology; LC3; Lymphocytes; Lymphocytes T; Male; Medical prognosis; Membrane Proteins - metabolism; Metastases; Microtubule-Associated Proteins - metabolism; Middle Aged; Mouth Neoplasms - immunology; Mouth Neoplasms - metabolism; Mouth Neoplasms - mortality; Mouth Neoplasms - pathology; Multivariate Analysis; Oral squamous cell carcinoma; Original; p62/SQSTM1; Phagocytosis; Proportional Hazards Models; Proteins; Sequestosome-1 Protein; Squamous cell carcinoma; Studies; T-Lymphocytes - immunology; Tumor cells
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12559

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. This work describes the correlation between the expression of autophagy‐related proteins and infiltration of immune cells in tumour microenvironment. The correlation observed between LC3 or p62/SQSTM1 and the infiltration of T cells suggests that autophagy may actively mobilise immune cells toward the cancer bed. Meanwhile, the three autophagy‐associated proteins examined were linked to the malignant potential and an unfavorable prognosis.