Abstract
Abstract Introduction: Autophagy is an endogenous process that degrades bulk proteins and organelles to maintain energy homeostasis under cellular stress and nutrient starvation. It has been still unclear whether autophagy promotes or suppresses tumor progression in various cancer patients. To date, several studies have shown that autophagy-related molecules such as LC3 and Beclin-1 play important roles in tumor progression; however, few studies regarding immunological significance of these autophagy components in tumor microenvironment exist. The objective of this study is to clarify association between the expression of autophagy-related proteins and immune infiltrates by immunohistochemistry (IHC). Patients and methods: Expression of two representative autophagy-associated molecules, LC3 and Beclin-1, and CD1a (dendritic cell), CD3 (T cell) and CD56 (NK cell) cells were examined by IHC in 74 patients with oral squamous cell carcinoma (OSCC). HLA class I heavy chain, HLA class II, Ki-67 and p53 were also stained and assessed. Two regions, central site and peripheral site in tumor tissues were evaluated, separately. Moreover, the association with various clinicopathological parameters including progression free and overall survival was evaluated. Results: LC3 and Beclin-1 were accumulated in both 27 of 74 cases (36.5%) OCCC examined. LC3 expression in peripheral margin was significantly associated with increasing dendritic cell (DC) and T cell infiltration. Interestingly, peripheral Beclin-1 expression showed statistically significant relation to increasing HLA class II expression on tumor cells. On the other hand, LC3 and Beclin-1 significantly correlates with several unfavorable clinicopathological parameters including short overall survival. In addition, LC3 and Beclin-1 expression in OSCC significantly related to lymphatic invasion by tumor cells. Conclusion: Significant association between LC3 and DC/T cell infiltration suggests that autophagy is likely to actively participate in immunological phenomena within tumor microenvironment. Furthermore, peripheral Beclin-1 may contribute to antigen presentation by tumor cells, while these two autophagy components also relates to unfavorable prognosis. Taken together, autophagy seems to promote immunogenicity of cancer cells, whereas it facilitates tumor progression. Citation Format: Koichi Sakakura, Hideyuki Takahashi, Kyoichi Kaira, Minoru Toyoda, Tetsunari Oyama, Kazuaki Chikamatsu. Expressions of autophagy-related proteins positively correlate with infiltration of immune cells and disease progression in oral squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 155. doi:10.1158/1538-7445.AM2014-155
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