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 &lt; 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.