Abstract 154: Immunological significance of p62/SQSTM1 accumulation in oral squamous cell carcinoma
Authors: Takahashi Hideyuki , Sakakura Koichi , Kaira Kyoichi , Toyoda Minoru , Oyama Tetsunari , Chikamatsu Kazuaki 
Published: May 2015

Abstract
Introduction: Autophagy is a prosurvival function that facilitates cellular response to stress by cleaning damaged proteins and organelles, and provides energy to the cells during starvation. p62/SQSTM1, which is a multifunctional, multi-domain scaffolding protein that has been implicated in various cell signaling pathways including autophagy-mediated protein degradation. In autophagy, an accumulation of ubiquitinated proteins retains p62/SQSTM1 in the cell, resulting in an increase of selective autophagy, whereas autophagy impairment can accumulate p62/SQSTM1. To date, evidence has accumulated that, in the tumor microenvironment, autophagy is known to play an important role in tumorigenesis, but also influences immune response to tumor cells. However, it still remains unknown how this autophagy-regulated protein, p62/SQSTM1 in tumor cells takes part in antitumor immune responses. To clarify the relation between the p62/SQSTM1 accumulation and antitumor immunity, we investigated the expression of p62/SQSTM1 and immune cell infiltration in tumor tissues obtained from patients with oral squamous cell carcinoma (OSCC).
Patients and methods: Seventy-four patients with OSCC who underwent curative surgical resection were included in this study. Tumor sections were stained by immunohistochemistry for p62/SQSTM1; dendritic cells (CD1a); T cells (CD3); NK cells (CD56); HLA class I heavy chain; HLA class II; Ki-67; p53. Each expression level was evaluated, and the association with clinicopathological factors was also determined.
Results: p62/SQSTM1 accumulation was observed in 24 of 74 (32.4 %) OSCC examined. The p62/SQSTM1 accumulation in tumor cells showed statistically significant positive correlation to HLA class I expression on tumor cells. Interestingly, in tumor margin regions, expression of p62/SQSTM1 in tumor cells was significantly associated with CD3+T cell infiltration, suggesting that anti-tumor specific T cells may infiltrate and recognize tumor cells as target cells. Moreover, p62/SQSTM1 accumulation in tumor cells was also significant correlated with vessel invasion by tumor cells.
Conclusion: In OSCC, p62/SQSTM1 accumulation in tumor cells was likely to associate with increase of tumor antigenicity, resulting in the mobilization of T cells toward cancer nest. On the other hand, p62/SQSTM1 accumulation in tumor cells may also contribute malignant potential in OSCC. Further elucidation of the role of p62/SQSTM1 in antitumor immunity through autophagy is currently underway.
Citation Format: Hideyuki Takahashi, Koichi Sakakura, Kyoichi Kaira, Minoru Toyoda, Tetsunari Oyama, Kazuaki Chikamatsu. Immunological significance of p62/SQSTM1 accumulation 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 154. doi:10.1158/1538-7445.AM2014-154