Tumor SQSTM1 (p62) expression and T cells in colorectal cancer

Keisuke Kosumi, Yohei Masugi, Juhong Yang, Zhi Rong Qian, Sun A. Kim, Wanwan Li, Yan Shi, Annacarolina da Silva, Tsuyoshi Hamada, Li Liu, Mancang Gu, Tyler S. Twombly, Yin Cao, David A. Barbie, Katsuhiko Nosho, Hideo Baba, Wendy S. Garrett, Jeffery A. Meyerhardt, Edward L. Giovannucci, Andrew T. ChanCharles S. Fuchs, Shuji Ogino, Reiko Nishihara

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Evidence suggests that activation of autophagy in neoplastic cells potentiates antitumor immunity through cross-presentation of tumor-associated antigens to T cells and release of immune mediators. The SQSTM1 (sequestosome 1, p62) protein is degraded by activated autophagy, and might enhance immune response to tumor cells. We hypothesized that tumor SQSTM1 expression level might be inversely associated with T-cell densities in colorectal carcinoma tissue. We evaluated tumor SQSTM1 expression by immunohistochemistry in 601 rectal and colon cancer cases within the Nurses' Health Study and Health Professionals Follow-up Study. Ordinal logistic regression analyses were conducted to assess the association of tumor SQSTM1 expression with CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ cell density in tumor tissue, controlling for potential confounders, including tumor status of microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation level, and KRAS, BRAF, and PIK3CA mutations. Tumor SQSTM1 expression level was inversely associated with FOXP3+ cell density (ptrend = 0.006), but not with CD3+, CD8+, or CD45RO+ cell density (with the adjusted α level of 0.01 for multiple hypothesis testing). For a unit increase in quartile categories of FOXP3+ cell density, multivariable odds ratios were 0.66 [95% confidence interval (CI), 0.45–0.98] for intermediate-level SQSTM1 expression, and 0.55 (95% CI, 0.36–0.83) for high-level SQSTM1 expression, compared with low-level SQSTM1 expression. Tumor SQSTM1 expression is inversely associated with FOXP3+ cell density in colorectal cancer tissue, suggesting a possible role of SQSTM1-expressing carcinoma cells on regulatory T cells in the tumor microenvironment.

Original languageEnglish
Article numbere1284720
JournalOncoImmunology
Volume6
Issue number3
DOIs
Publication statusPublished - 2017 Mar 4
Externally publishedYes

Keywords

  • Adenocarcinoma
  • colorectum
  • immunoprevention
  • immunotherapy
  • molecular pathology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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  • Cite this

    Kosumi, K., Masugi, Y., Yang, J., Qian, Z. R., Kim, S. A., Li, W., Shi, Y., da Silva, A., Hamada, T., Liu, L., Gu, M., Twombly, T. S., Cao, Y., Barbie, D. A., Nosho, K., Baba, H., Garrett, W. S., Meyerhardt, J. A., Giovannucci, E. L., ... Nishihara, R. (2017). Tumor SQSTM1 (p62) expression and T cells in colorectal cancer. OncoImmunology, 6(3), [e1284720]. https://doi.org/10.1080/2162402X.2017.1284720