PT  - JOURNAL ARTICLE
AU  - Mima, Kosuke
AU  - Nishihara, Reiko
AU  - Nowak, Jonathan A.
AU  - Kim, Sun A.
AU  - Song, Mingyang
AU  - Inamura, Kentaro
AU  - Sukawa, Yasutaka
AU  - Masuda, Atsuhiro
AU  - Yang, Juhong
AU  - Dou, Ruoxu
AU  - Nosho, Katsuhiko
AU  - Baba, Hideo
AU  - Giovannucci, Edward L.
AU  - Bowden, Michaela
AU  - Loda, Massimo
AU  - Giannakis, Marios
AU  - Bass, Adam J.
AU  - Dranoff, Glenn
AU  - Freeman, Gordon J.
AU  - Chan, Andrew T.
AU  - Fuchs, Charles S.
AU  - Qian, Zhi Rong
AU  - Ogino, Shuji
TI  - MicroRNA <em>MIR21</em> and T Cells in Colorectal Cancer
AID  - 10.1158/2326-6066.CIR-15-0084
DP  - 2016 Jan 01
TA  - Cancer Immunology Research
PG  - 33--40
VI  - 4
IP  - 1
4099  - http://cancerimmunolres.aacrjournals.org/content/4/1/33.short
4100  - http://cancerimmunolres.aacrjournals.org/content/4/1/33.full
SO  - Cancer Immunol Res2016 Jan 01; 4
AB  - 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 α level to 0.012 for multiple hypothesis testing. Tumor MIR21 expression was inversely associated with densities of CD3+ and CD45RO+ cells (Ptrend < 0.0005). The multivariate odds 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. Cancer Immunol Res; 4(1); 33–40. ©2015 AACR.