Lo C.-H.Lee S.-C.Wu P.-Y.Pan W.-Y.Su J.Cheng C.-W.Roffler S.R.BOR-LUEN CHIANGLee C.-N.Wu C.-W.Tao M.-H.2021-07-022021-07-0220030022-1767https://www.scopus.com/inward/record.uri?eid=2-s2.0-0037769934&doi=10.4049%2fjimmunol.171.2.600&partnerID=40&md5=268e43408285646425f4f88fb7742ce3https://scholars.lib.ntu.edu.tw/handle/123456789/568037The structure and T cell stimulatory effects of the recently discovered cytokine IL-23 are similar to, but distinct from, those of IL-12. Although the antitumor activities of IL-12 are well characterized, the effect of IL-23 on tumor growth is not known. In this study, murine CT26 colon adenocarcinoma and B16F1 melanoma cells were engineered using retroviral vectors to release single-chain IL-23 (scIL-23) to evaluate its antitumor activity. In BALB/c mice, scIL-23-transduced CT26 cells grew progressively until day 26 to an average size of 521 ± 333 mm3, then the tumors started to regress in most animals, resulting in a final 70% rate of complete tumor rejection. scIL-23 transduction also significantly suppressed lung metastases of CT26 and B16F1 tumor cells. In addition, mice that rejected scIL-23-transduced tumors developed a memory response against subsequent wild-type tumor challenge. Compared with scIL-12-expressing CT26 cells, scIL-23-transduced tumors lacked the early response, but achieved comparable antitumor and antimetastatic activity. These results demonstrated that IL-23, like IL-12, provided effective protection against malignant diseases, but it probably acted by different antitumor mechanisms. As a first step in identifying these antitumor mechanisms, tumor challenge studies were performed in immunocompromised hosts and in animals selectively depleted of various lymphocyte populations. The results showed that CD8+ T cells, but not CD4+ T cells or NK cells, were crucial for the antitumor activity of IL-23.[SDGs]SDG3cytokine; interleukin 12; interleukin 23; retrovirus vector; single chain interleukin 23; unclassified drug; animal cell; animal model; animal tissue; antineoplastic activity; article; cancer cell culture; cell growth; cell size; cell strain B16F1; cell strain CT26; chemical structure; colon adenocarcinoma; cytokine release; female; genetic engineering; genetic transduction; humoral immunity; immune deficiency; immunological memory; lymphocyte depletion; lymphocyte subpopulation; melanoma cell; metastasis inhibition; mouse; natural killer cell; nonhuman; priority journal; T lymphocyte activation; T lymphocyte subpopulation; tumor growth; tumor regression; tumor rejectionjournal article10.4049/jimmunol.171.2.600128472242-s2.0-0037769934