{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:44:34Z","timestamp":1791877474875,"version":"4.3.4"},"reference-count":71,"publisher":"National Academy of Sciences","issue":"44","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["1R35 GM134864"],"award-info":[{"award-number":["1R35 GM134864"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,10,29]]},"abstract":"<jats:p>\n                    Chimeric antigen receptor T cell therapies have achieved great success in eradicating some liquid tumors, whereas the preclinical results in treating solid tumors have proven less decisive. One of the principal challenges in solid tumor treatment is the physical barrier composed of a dense extracellular matrix, which prevents immune cells from penetrating the tissue to attack intratumoral cancer cells. Here, we improve immune cell infiltration into solid tumors by manipulating septin-7 functions in cells. Using protein allosteric design, we reprogram the three-dimensional structure of septin-7 and insert a blue light-responsive light-oxygen-voltage-sensing domain 2 (LOV2), creating a light-controllable septin-7-LOV2 hybrid protein. Blue light inhibits septin-7 function in live cells, inducing extended cell protrusions and cell polarization, enhancing cell transmigration efficiency through confining spaces. We genetically edited human natural killer cell line (NK92) and mouse primary CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells expressing the engineered protein, and we demonstrated improved penetration and cytotoxicity against various tumor spheroid models. Our proposed strategy to enhance immune cell infiltration is compatible with other methodologies and therefore, could be used in combination to further improve cell-based immunotherapies against solid tumors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2405717121","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T11:45:51Z","timestamp":1729683951000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["Optogenetically engineered Septin-7 enhances immune cell infiltration of tumor spheroids"],"prefix":"10.1073","volume":"121","author":[{"given":"Jiaxing","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Hnath","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033"},{"name":"Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5301-9459","authenticated-orcid":false,"given":"Congzhou M.","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033"},{"name":"Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA 16802"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Beidler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6788-6518","authenticated-orcid":false,"given":"Todd D.","family":"Schell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8225-4025","authenticated-orcid":false,"given":"Nikolay V.","family":"Dokholyan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033"},{"name":"Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802"},{"name":"Department of Biochemistry &amp; Molecular Biology, Penn State College of Medicine, Hershey, PA 17033"},{"name":"Department of Chemistry, Pennsylvania State University, University Park, PA 16802"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14235983"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2014.05.019"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00453"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.936496"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-022-04547-4"},{"key":"e_1_3_4_6_2","first-page":"1","article-title":"Clinical investigations of CAR-T cell therapy for solid tumors","volume":"13","author":"Chen K.","year":"2022","unstructured":"K. Chen , Clinical investigations of CAR-T cell therapy for solid tumors. Front. Immunol. 13, 1\u201312 (2022).","journal-title":"Front. Immunol."},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14215351"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21708"},{"key":"e_1_3_4_9_2","first-page":"451","article-title":"Global cancer statistics 2022: The trends projection analysis","volume":"10","author":"Chhikara B. S.","year":"2023","unstructured":"B. S. Chhikara, K. Parang, Global cancer statistics 2022: The trends projection analysis. Chem. Biol. Lett. 10, 451 (2023).","journal-title":"Chem. Biol. Lett."},{"key":"e_1_3_4_10_2","first-page":"508","article-title":"Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors","volume":"23","author":"Chen T.","year":"2023","unstructured":"T. Chen , Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors. Bioact. Mater. 23, 508\u2013523 (2023).","journal-title":"Bioact. Mater."},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-006401"},{"key":"e_1_3_4_12_2","first-page":"14173","article-title":"Thermosusceptible nitric-oxide-releasing nitrogel for strengthening antitumor immune responses with tumor collagen diminution and deep tissue delivery during NIR laser-assisted photoimmunotherapy","volume":"15","author":"Mohapatra A.","year":"2023","unstructured":"A. Mohapatra , Thermosusceptible nitric-oxide-releasing nitrogel for strengthening antitumor immune responses with tumor collagen diminution and deep tissue delivery during NIR laser-assisted photoimmunotherapy. ACS Appl. Mater. Interfaces 15, 14173\u201314183 (2023).","journal-title":"ACS Appl. Mater. 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D.","year":"2001","unstructured":"T. D. Schell, S. S. Tevethia, \u201cCytotoxic T lymphocytes in SV40 Infections\u201d in SV40 Protocols. L. Raptis, Eds. 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