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Previously, we developed a novel OAd fully composed of human adenovirus serotype 35 (OAd35). OAd35 efficiently killed a variety of human tumor cells; however, OAd35-mediated activation of antitumor immunity remains to be evaluated. In this study, we examined whether OAd35-induced activation of immune cells contributes to the antitumor effects of OAd35.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Tumor infiltration and activation of immune cells following intratumoral administration of OAd35 in tumor-bearing immune-competent and nude mice were analyzed. The involvement of immune cells in the tumor growth-suppression effects of OAd35 was evaluated in asialo GM1 (aGM1)\n                      <jats:sup>+<\/jats:sup>\n                      cell-depleted mice. The key signals for the OAd35-mediated tumor infiltration of NK cells were examined in interferon (IFN) alpha and beta receptor subunit 1 (IFNAR1) knockout and toll-like receptor 9 knockout mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OAd35 efficiently induced tumor infiltration of activated natural killer (NK) cells and T cells after intratumoral administration in B16 tumor-bearing mice. Depletion of aGM1\n                      <jats:sup>+<\/jats:sup>\n                      cells, including NK cells and a portion of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, significantly hindered the OAd35-mediated tumor growth suppression in C57BL\/6J wild-type mice and BALB\/c nude mice. In IFNAR1 knockout mice, OAd35-induced tumor infiltration of activated NK cells and OAd35-mediated tumor growth suppression were significantly attenuated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These data described above suggested that immune cells, including aGM1\n                      <jats:sup>+<\/jats:sup>\n                      cells, contributed to the antitumor effects of OAd35. OAd35 significantly promoted activation and tumor infiltration of NK cells. The type-I IFN signal was crucial for the OAd35-mediated tumor infiltration, activation of NK cells, and tumor growth suppression. These findings suggest that OAd35 is a promising cancer immunotherapy agent via its enhancement of the antitumor activities of immune cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2022-006558","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T01:41:22Z","timestamp":1752198082000},"page":"e006558","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Oncolytic adenovirus serotype 35 mediated tumor growth suppression\n                    <i>via<\/i>\n                    efficient activation of antitumor immunity"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3532-7949","authenticated-orcid":false,"given":"Ryosuke","family":"Ono","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, The University of Osaka, Osaka, 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