class I T (Munz, autophagy (Argiris, 2008) 30 5 (Jemal, 2009) autophagy HLA / 4 21 (Sakakura, 2007; Chikamatsu, 2008; Chikamatsu, 2009) in vitro

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2 65 35 (Argiris, 2008)30 5 (Jemal, 2009) / 1991Boon / 4 21 (Sakakura, 2007; Chikamatsu, 2008; Chikamatsu, 2009) / / (Sakakura, 2005; Sakakura, 2006; Sakakura, 2007; Chikamatsu, 2007; Chikamatsu, 2008)/ (Ferrone, 2007; Sakakura, 2006) autophagy autophagy (White, 2009)autophagy 2005 Blum Munz autophagy HLA class II (T ) autophagy HLA class II class I T (Munz, 2010) autophagy autophagy () autophagy in vitro 2 in vivo (1)1: in vitro IFN- serum free media starved condition Beclin1 LC3 autophagy (Wan, 2010; Crotzer, 2009) HLA class I (classical/ non-classical; Campoli, 2008)/ class II (Reith, 2006) (APM) flow cytometry (FCM) autophagy RNAi / / Allo CD4+/CD8+T in vitro stimulation (IVS) IVS T ELISPOT assay flow cytometry (FCM) (Sakakura, 2007; Chikamatsu, 2009) in vitro/ex vivo

3 CD3+T CD56 (2)2: in vivo natural killer (NK) (FFPE)Beclin1 LC3 autophagy HLA class I/II APM 74 LC3 27 (36.5%) FFPE APM Beclin-1 27 (36.5%)p62/SQSTM1 24 (32.4%) (Wang, 2005) LC3 p62/sqstm1 IL-10 TGF- T (LC3: p=0.0345, p62: p=0.0084, ) IFN- microenvironment HLA autophagy p53 (Chikamatsu, 2009; Sakakura, 2007) p53 HLA-A2 A24 DP5 CD4+/CD8+T p53 ELISPOT (1) In vitro Gun-1, HSC-3 autophagy 2 western blotting autophagy LC3-II autophagy HLA class I, HLA-DR, PD-L1, PD-L2, CD44, CD133 FCM HLA class I autophagy class II PD-L1, PD-L2 CD44 In vitro autophagy in vivo autophagy (2) In vivo autophagy 74 FFPE autophagy LC3 autophagy pathway Beclin-1, p62/sqstm1hla class I, class II CD1a p62/sqstm1 HLA class I (p=0.0029)beclin-1 HLA class II (p=0.0362) () LC3 (p= )(p= ) (p= ) Ki-67 (p=0.0187)beclin-1 (p= )p62/sqstm1 (p=0.0426)(p=0.0127)

4 LC3 (p=0.030) LC3 (p=0.0305, ) autophagy autophagy T regulatory T cell Cancer Science 2015 Autophagy (M) Don t eat me signal CD47 MCD68 M2 CD Beclin-1 CD47 (p= )lc3 p62/sqstm1 M (LC3: rs=0.418, p=0.0009; p62: rs=0.300, p= )m2 (LC3: rs=0.321, p= ; p62: rs=0.368, p= ) (3) FFPE LAT1-CD98ASCT2xCT LAT1 Br J Cancer (HDACi) / HDACi 5 Sakakura K, Takahashi H, Kaira K, Immunological significance of the accumulation of autophagy components in oral squamous cell carcinoma.cancer Sci Jan;106(1):1-8. Toyoda M, Kaira K, Shino M, Sakakura K, Takahashi K, Takayasu Y, Tominaga H, Oriuchi N, Nikkuni O, Suzuki M, Iijima M, Tsukamoto N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K. CD98 as a novel prognostic indicator for patients with stage III/IV hypopharyngeal squamous cell carcinoma. Head Neck Jun 10. doi: /hed [Epub ahead of print] Toyoda M, Kaira K, Ohshima Y, Ishioka NS, Shino M, Sakakura K, Takayasu Y, Takahashi K, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K. Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xct) in surgically resected tongue cancer. Br J Cancer May 13;110(10): Chikamatsu K, Ishii H, Murata T, Sakakura K, Shino M, Toyoda M, Takahashi K, Masuyama K. Alteration of cancer stem cell-like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck. Cancer Sci Nov;104(11): Kaira K, Toyoda M, Shino M, Sakakura K, Takahashi K, Tominaga H, Oriuchi N, Kanai Y, Oyama T, Chikamatsu K. Clinicopathological significance of L-type amino acid transporter 1 (LAT1) expression in patients with adenoid cystic carcinoma. Pathol Oncol Res Oct;19(4): Sakakura K, Takahashi H, Kaira K, Immunological significance of p62/sqstm1 accumulation in oral squamous cell carcinoma. 5th World Congress of International Federation of Head and Neck Oncologic Societies, 2014 Annual Meeting of American Head and Neck Society; 2014 July 25-31; New York City, NY, USA Sakakura K, Takahashi H, Kaira K, Expressions of autophagy-related proteins positively correlate with infiltration of immune cells and disease progression in oral squamous cell carcinoma [abstract]. Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA,

5 USA. AACR; Abstract nr 155. Takahashi H, Sakakura K, Kaira K, Immunological significance of p62/sqstm1 accumulation in oral squamous cell carcinoma [abstract]. Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA, USA. AACR; Abstract nr autophagy ,,. autophagy ,,