@article{oai:showa.repo.nii.ac.jp:00000682, author = {OMORI, Risa and EGUCHI, Junichi and HIROISHI, Kazumasa and ISHII, Shigeaki and SASAGAWA, Ayako and SAKAKI, Masashi and DOI, Hiroyoshi and KAJIWARA, Atsushi and IMAWARI, Michio}, issue = {2}, journal = {The Showa University journal of medical sciences}, month = {2012-06, 2019-07-26}, note = {Interleukin (IL)-4 exhibits strong antitumor effects and IL-4 gene therapy has been used clinically in the treatment of some types of cancer. In the present study, we evaluated the efficacy of IL-4-transduced tumor cell vaccines in combination with blockade of programmed cell death 1 (PD-1) and investigated the mechanisms underlying the antitumor effects of this therapy. A poorly immunogenic murine colorectal cancer cell line (i.e. MC38) was transduced to overexpress IL-4. In a therapeutic model, MC38-IL4 cells and anti-PD-1 antagonistic antibodies (Ab) were inoculated into parental tumor-bearing mice. Immunohistochemical analyses and tumor-specific lysis were also performed. Additive antitumor effects were observed when mice were treated with IL-4 in combination with an anti-PD-1 Ab. Immunohistochemical analysis of the therapeutic model showed marked infiltration of CD4+ and CD8+ cells into established MC38 tumors of mice treated with anti-PD-1 Ab. Significant tumor-specific cytolysis was detected when the splenocytes of mice treated with both IL-4 and anti-PD-1 Ab were used as effector cells. These results suggest that blockade of the interaction between PD-1 and programmed death ligand 1 (PD-L1) enhances the antitumor immune responses induced by IL-4. Thus, IL-4 gene-transduced tumor cell vaccines in combination with PD-1 blockade may be considered as possible candidates for clinical trials of new cancer vaccines.}, pages = {127--137}, title = {Effects of Interleukin-4-Transduced Tumor Cell Vaccines and Blockade of Programmed Cell Death 1 on the Growth of Established Tumors}, volume = {24}, year = {} }