{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:57:04Z","timestamp":1762084624430,"version":"build-2065373602"},"reference-count":106,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["CA253069","PSC-CUNY 52","R01GM123508","TRADB-49-271"],"award-info":[{"award-number":["CA253069","PSC-CUNY 52","R01GM123508","TRADB-49-271"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CUNY University Committee on Research Awards","award":["CA253069","PSC-CUNY 52","R01GM123508","TRADB-49-271"],"award-info":[{"award-number":["CA253069","PSC-CUNY 52","R01GM123508","TRADB-49-271"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA253069","PSC-CUNY 52","R01GM123508","TRADB-49-271"],"award-info":[{"award-number":["CA253069","PSC-CUNY 52","R01GM123508","TRADB-49-271"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Professional Staff Congress-City University of New York","award":["CA253069","PSC-CUNY 52","R01GM123508","TRADB-49-271"],"award-info":[{"award-number":["CA253069","PSC-CUNY 52","R01GM123508","TRADB-49-271"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The standard of care for most malignant solid tumors still involves tumor resection followed by chemo- and radiation therapy, hoping to eliminate the residual tumor cells. This strategy has been successful in extending the life of many cancer patients. Still, for primary glioblastoma (GBM), it has not controlled recurrence or increased the life expectancies of patients. Amid such disappointment, attempts to design therapies using the cells in the tumor microenvironment (TME) have gained ground. Such \u201cimmunotherapies\u201d have so far overwhelmingly used genetic modifications of Tc cells (Car-T cell therapy) or blocking of proteins (PD-1 or PD-L1) that inhibit Tc-cell-mediated cancer cell elimination. Despite such advances, GBM has remained a \u201cKiss of Death\u201d for most patients. Although the use of innate immune cells, such as the microglia, macrophages, and natural killer (NK) cells, has been considered in designing therapies for cancers, such attempts have not reached the clinic yet. We have reported a series of preclinical studies highlighting strategies to \u201cre-educate\u201d GBM-associated microglia and macrophages (TAMs) so that they assume a tumoricidal status. Such cells then secrete chemokines to recruit activated, GBM-eliminating NK cells and cause the rescue of 50\u201360% GBM mice in a syngeneic model of GBM. This review discusses a more fundamental question that most biochemists harbor: \u201csince we are generating mutant cells in our body all the time, why don\u2019t we get cancer more often?\u201d The review visits publications addressing this question and discusses some published strategies for re-educating the TAMs to take on the \u201csentry\u201d role they initially maintained in the absence of cancer.<\/jats:p>","DOI":"10.3390\/ijms24055026","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T04:29:58Z","timestamp":1678076998000},"page":"5026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Why Don\u2019t the Mutant Cells That Evade DNA Repair Cause Cancer More Frequently? Importance of the Innate Immune System in the Tumor Microenvironment"],"prefix":"10.3390","volume":"24","author":[{"given":"Shubhasmita","family":"Mohapatra","sequence":"first","affiliation":[{"name":"Department of Chemistry, The College of Staten Island, City University of New York, Staten Island, NY 10314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared","family":"Cafiero","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The College of Staten Island, City University of New York, Staten Island, NY 10314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4060-7283","authenticated-orcid":false,"given":"Khosrow","family":"Kashfi","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY 10031, USA"},{"name":"Graduate Program in Biology, City University of New York Graduate Center, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parag","family":"Mehta","sequence":"additional","affiliation":[{"name":"Aveta Biomics, Inc., 110 Great Road, Suite 302, Bedford, MA 01730, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Probal","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The College of Staten Island, City University of New York, Staten Island, NY 10314, USA"},{"name":"Graduate Program in Biology, City University of New York Graduate Center, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00401-005-0991-y","article-title":"Epidemiology and etiology of gliomas","volume":"109","author":"Ohgaki","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_2","first-page":"114","article-title":"Practical guidelines for the treatment of malignant gliomas","volume":"168","author":"Chamberlain","year":"1998","journal-title":"West. 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