Correction to: miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy

The original article [1] contains a spelling error in the authorship; the authors would like to note the correct spelling of the second author, Jiajia Xi

miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy

Abstract Background Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting step in converting tryptophan to kynurenine. Chimeric antigen receptor (CAR) T cells are T cells with recombinant receptors targeting tumor-associated antigens. The Food and Drug Administration has approved CAR T cells that target CD19 for treatment of advanced B cell leukemia and lymphoma. However, CAR T cell therapy in solid tumors has been hampered by multiple obstacles. Preclinical and clinical studies suggest that combinatorial immune checkpoint blockade and IDO1 inhibition provide durable therapeutic efficacy against cancer. Yet, the combination of IDO1 inhibition and CAR T has not been attempted. Methods We analyze IDO1 downregulation by miR-153 in colon cancer cells and the association of IDO1 and miR-153 expression with colorectal patient survival. We generate CAR T cells targeting the epidermal growth factor receptor variant III and measure their tumor killing effects against colon cancer cells with or without miR-153 overexpression by killing assays and in xenografts. Results IDO1 is highly expressed in colorectal tumors and is inversely associated with patient survival. miR-153 directly inhibits IDO1 expression by targeting its 3′ untranslated region in colon cancer cells; yet, miR-153 overexpression does not affect cancer cell survival, apoptosis, and colony formation. When colon cancer cells are targeted by CAR T cells, miR-153 overexpression within tumor cells significantly enhances T cell killing in vitro and suppresses xenograft tumor growth in mice. Conclusions These findings indicate that miR-153 inhibits IDO1 expression in colon cancer cells and is a tumor-suppressive miRNA that enhances CAR T cell immunotherapy. This study supports the combinatorial use of IDO1 inhibitors and CAR T cells in treating solid tumors

Additional file 4: of miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy

Figure S4. IDO1 downregulation by miR-153 is inducer and time independence. (A and B) IDO1 expression in DLD-1 cells treated by Cp-G DNA or LPS was down-regulated by miR-153 as measured by flow cytometry (A) or by western blotting (B). DLD-1 cells were treated with LPS or cp-G DNA for 12 h. (C and D) The IDO1 protein (C) or mRNA (D) levels in DLD-1 and HCT-116 cells transfected with or without miR-153 before treated with LPS for 6 to 24 h. (PDF 309 kb

Additional file 3: of miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy

Figure S3. miRNAs are predicted to target the IDO1 3' UTR. (A) Schematic representation of the pmirGLO vector carrying two dual luciferase genes and the IDO1 3' UTR. (B and C) Dual luciferase assays from 293T cells (B) or Hela cells (C) transfected with miR-153 and the pmirGLO construct. (PDF 189 kb

Additional file 5: of miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy

Figure S5. The activation of T cells exhibits no difference when co-cultured with tumor cells with or without miR-153. T cells were co-cultured in DLD-1+miR-153 (orange) or DLD-1+NC cells (green) for 24 hours. The expression of the designated T cell activation markers was measured by flow cytometry. (PDF 206 kb

Additional file 1: of miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy

Figure S1. IDO1 was induced by IFN-γ. IDO1 was induced by IFN-γ. (A) IDO1 expression of A549 and DLD-1 stimulated by 1-300 ng/ml IFN-γ for 24 h. IDO1 expression was measured using flow cytometry. (B) IDO1 expression in DLD-1 cells treated with 30 ng/ml IFN-γ for 3-48h. (C) IDO1 expression curves plotted from data in (A) and (B). (PDF 368 kb

Additional file 2: of miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy

Figure S2. IDO2 and TDO expression in relationship to survival of patients with colorectal cancer. (A) Overall survival of patients with colon cancer (n = 382) in the TCGA database. Patients were classified as having high or low IDO2 (left) or TDO (right) expression according the median level. (B) Survival in days according to IDO2 expression level of patients in Panel A. (PDF 266 kb