miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer

Abstract

MicroRNAs (miRNAs/miRs) regulate the levels of transcripts and serve a critical function in the regulation of tumor microenvironments. Therefore, miRNA levels in cancer tissues are thought to be potential biomarkers for immunotherapy. From a phase I trial of a vaccine treatment using 5 human leukocyte antigen (HLA)-A*2402-restricted peptides (registration no. UMIN000004948), colorectal cancer (CRC) tissues were obtained from 8 patients and normal colorectal tissues from 5 patients via surgery. From a phase II trial using the same peptides (registration no. UMIN000001791), CRC tissues were obtained from 16 patients from the HLA-A*2402-matched group and 10 patients from the HLA-A*2402-unmatched group. These tissues were used for miRNA microarray analysis. As the first step, cancer tissues from the phase I study were used and 10 candidate miRNAs were selected by comparing the miRNA expression between two groups; one with improved prognosis and the other with poor prognosis. The miRNAs were subsequently validated using the cases enrolled in the phase II study. Significantly improved prognoses were identified in 16 patients in the HLA-A*2402-matched group with high expression of miR-196b-5p and low expression of miR-378a-3p and miR-486-5p. There was no difference in prognosis in the 10 patients in the HLA-A*2402-unmatched group. Therefore, high miR-196b expression and low miR-378a-3p and miR-486-5p expression were indicated as useful biomarkers for prediction of the efficacy of vaccine treatment for patients with metastatic CRC. In a planned phase III study, expression levels of these 3 miRNAs (miR-196b-5p, miR-378a-3p and miR-486-5p) may be useful biomarkers for assessing patients who are likely to have an improved outcome following vaccination.

miR‐125b‐1 and miR‐378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer

“…The purpose of the present study was to explore miRNAs as novel predictive biomarkers for the efficacy of immunotherapies before their treatment. We previously reported that three miRNAs might be useful biomarkers . As the cellular origin is crucial for determination of miRNAs, in the present study, we used LCM to separate cancer cells and stromal cells for miRNA analysis.…”

“…We previously reported that three miRNAs might be useful biomarkers. (25) As the cellular origin is crucial for determination of miRNAs, in the present study, we used LCM to separate cancer cells and stromal cells for miRNA analysis. Here we demonstrate the results of miRNA microarray analysis and qRT-PCR in CRC cancer and stromal cells.…”

Assessment by miRNA microarray of an autologous cancer antigen‐pulsed adoptive immune ensemble cell therapy (AC‐ACT) approach; demonstrated induction of anti‐oncogenic and anti‐PD‐L1 miRNAs

“…miR‐320a, another prominently decreased by AC‐ACT, suppresses colorectal cancer progression by targeting Rac1, although high miR‐320a levels appear to induce pro‐tumorigenic M2‐like macrophages . Low miR‐320a which we observe with AC‐ACT has also been associated with positive efficacy of peptide vaccination for colorectal cancer . These counteractive functions, cancer suppressive and immune inhibition, are seen for other miRNAs such as miR‐21 and miR‐155 and underscore the need for further studies.…”

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

“…Another study [87] provides further evidence of the capacity of miRNA-486 to influence treatment outcomes, showing that colorectal cancer (CRC) patients treated with a vaccine using 5 epitope peptides were more likely to have an improved prognosis if the tumors exhibited low miRNA-486 expression levels.…”