MicroRNA MIR21 and T cells in colorectal cancer

Authors

Kosuke Mima, Harvard Medical School
Reiko Nishihara, Harvard Medical School
Jonathan A. Nowak, Brigham and Women's Hospital
Sun A. Kim, Harvard Medical School
Mingyang Song, Harvard T.H. Chan School of Public Health
Kentaro Inamura, Harvard Medical School
Yasutaka Sukawa, Harvard Medical School
Atsuhiro Masuda, Harvard Medical School
Juhong Yang, Harvard Medical School
Ruoxu Dou, Harvard Medical School
Katsuhiko Nosho, Sapporo Medical University School of Medicine
Hideo Baba, Graduate School of Medical Sciences
Edward L. Giovannucci, Harvard T.H. Chan School of Public Health
Michaela Bowden, Harvard Medical School
Massimo Loda, Harvard Medical School
Marios Giannakis, Harvard Medical School
Adam J. Bass, Harvard Medical School
Glenn Dranoff, Harvard Medical School
Gordon J. Freeman, Harvard Medical School
Andrew T. Chan, Brigham and Women's Hospital
Charles S. Fuchs, Harvard Medical School
Zhi Rong Qian, Harvard Medical School
Shuji Ogino, Harvard Medical School

Document Type

Journal Article

Publication Date

1-1-2016

Journal

Cancer Immunology Research

Volume

4

Issue

1

DOI

10.1158/2326-6066.CIR-15-0084

Abstract

© 2015 American Association for Cancer Research. The complex interactions between colorectal neoplasia and immune cells in the tumor microenvironment remain to be elucidated. Experimental evidence suggests that microRNA MIR21 (miR-21) suppresses antitumor T-cell-mediated immunity. Thus, we hypothesized that tumor MIR21 expression might be inversely associated with T-cell density in colorectal carcinoma tissue. Using 538 rectal and colon cancer cases from the Nurses' Health Study and the Health Professionals Follow-up Study, we measured tumor MIR21 expression by a quantitative reverse-transcription PCR assay. Densities of CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ cells in tumor tissue were determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Ordinal logistic regression analysis was conducted to assess the association of MIR21 expression (ordinal quartiles as a predictor variable) with T-cell density (ordinal quartiles as an outcome variable), adjusting for tumor molecular features, including microsatellite instability; CpG island methylator phenotype; KRAS, BRAF, and PIK3CA mutations; and LINE-1 methylation. We adjusted the two-sided a level to 0.012 for multiple hypothesis testing. Tumor MIR21 expression was inversely associated with densities of CD3+ and CD45RO+ cells (Ptrend < 0.0005). Themultivariateodds ratio of the highest versus lowest quartile of MIR21 for a unit increase in quartile categories of CD3+ or CD45RO+ cells was 0.44 [95% confidence interval (CI), 0.28 to 0.68] or 0.41 (95% CI, 0.26-0.64), respectively. Our data support a possible role of tumor epigenetic deregulation by noncoding RNA in suppressing the antitumor T-cell-mediated adaptive immune response and suggest MIR21 as a potential target for immunotherapy and prevention in colorectal cancer.

APA Citation

Mima, K., Nishihara, R., Nowak, J., Kim, S., Song, M., Inamura, K., Sukawa, Y., Masuda, A., Yang, J., Dou, R., Nosho, K., Baba, H., Giovannucci, E., Bowden, M., Loda, M., Giannakis, M., Bass, A., Dranoff, G., Freeman, G., Chan, A., Fuchs, C., Qian, Z., & Ogino, S. (2016). MicroRNA MIR21 and T cells in colorectal cancer. Cancer Immunology Research, 4 (1). http://dx.doi.org/10.1158/2326-6066.CIR-15-0084