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

Sakakura, Koichi, Takahashi, Hideyuki, Kaira, Kyoichi, Toyoda, Minoru, Oyama, Tetsunari, Chikamatsu, Kazuaki·2015·Cancer Science
DOI 10.1111/cas.12559PMC PMC4317780
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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, LC 3, Beclin‐1 and p62/SQSTM 1, 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 LC 3 and p62/SQSTM 1 in the peripheral site significantly correlated with an increase in the infiltration of T cells. Furthermore, the expression of p62/SQSTM 1 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 LC 3 in the peripheral site. The correlation observed between LC 3 or p62/SQSTM 1 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.

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Figure 1 (a) Representative immunohistochemistry (IHC) staining of LC3, Beclin-1 and p62 (×400 magnification), according to the intensity scores. All pictures were taken under the same photographic condition. LC3 and p62 SQSTM1 were expressed in puncta corresponding to autophagosomes in the cytoplasm. Beclin-1 was mainly expressed in the cytoplasm. (b) Representative CD1a+ DC, CD3+ T cell, CD56+ NK cell, HLA class I heavy chain and class II stainings were presented under magnification of ×400. HLA class I heavy chain and class II were presented as a membranous pattern.
Figure 1 (a) Representative immunohistochemistry (IHC) staining of LC3, Beclin-1 and p62 (×400 magnification), according to the intensity scores. All pictures were taken under the same photographic condition. LC3 and p62 SQSTM1 were expressed in puncta corresponding to autophagosomes in the cytoplasm. Beclin-1 was mainly expressed in the cytoplasm. (b) Representative CD1a+ DC, CD3+ T cell, CD56+ NK cell, HLA class I heavy chain and class II stainings were presented under magnification of ×400. HLA class I heavy chain and class II were presented as a membranous pattern.CC BY-NC-ND · PubMed Central
Figure 2 Representative serial immunohistochemistry (IHC) pictures of the expressions of molecules which showed statistically significant association each other. (a) LC3 and p62/SQSTM1 significantly correlated with CD3+ T cell infiltration. (b) p62/SQSTM1 was closely related to the expression of HLA class I. (c) Beclin-1 was significantly related to HLA class II expression.
Figure 2 Representative serial immunohistochemistry (IHC) pictures of the expressions of molecules which showed statistically significant association each other. (a) LC3 and p62/SQSTM1 significantly correlated with CD3+ T cell infiltration. (b) p62/SQSTM1 was closely related to the expression of HLA class I. (c) Beclin-1 was significantly related to HLA class II expression.CC BY-NC-ND · PubMed Central
Figure 3 The log-rank test revealed that the positive expression of LC3 in the peripheral site of the tumor led to a significantly shorter survival. Multivariate regression analysis also identified the peripheral expression of LC3 as an independent prognostic factor (P = 0.034).
Figure 3 The log-rank test revealed that the positive expression of LC3 in the peripheral site of the tumor led to a significantly shorter survival. Multivariate regression analysis also identified the peripheral expression of LC3 as an independent prognostic factor (P = 0.034).CC BY-NC-ND · PubMed Central

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Metadata

Authors
Sakakura, K., Takahashi, H., Kaira, K., Toyoda, M., Oyama, T., & Chikamatsu, K.
Affiliations
  • Department of Otolaryngology – Head and Neck Surgery Gunma University Graduate School of Medicine Gunma Japan
  • Department of Oncology Clinical Development Gunma University Graduate School of Medicine Gunma Japan
  • Department of Diagnostic Pathology Gunma University Graduate School of Medicine Gunma Japan
Venue
Cancer Science
Publisher
Wiley
Published
2014-12-08
Volume
106
Issue
1
Pages
1-8
ISSN
  • 1347-9032
  • 1349-7006
DOI
10.1111/cas.12559
PMC
PMC4317780
Cited by
40
References
1
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Funders
Grants-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology, Japan (24791820)

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