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Neuroendocrine phenotype correlates with invasiveness, metastasis, and low survival rates. This work evaluated the effect of neuroendocrine differentiation of adenocarcinoma on the mouse immune system. A549 cells were treated with FSK (forskolin) and IBMX (3-Isobutyl-1-methylxanthine) for 96 h to induce neuroendocrine differentiation (NED). Systemic effects were assessed by determining changes in circulating cytokines and immune cells of BALB\/c mice immunized with PBS, undifferentiated A549 cells, or neuroendocrine A549NED cells. A549 cells increased circulating monocytes, while CD4+CD8\u2212 and CD4+CD8+ T cells increased in mice immunized with neuroendocrine cells. IL-2 and IL-10 increased in mice that received untreated A549 cells, suggesting that the immune system mounts a regulated response against adenocarcinoma, which did not occur with A549NED cells. Cocultures demonstrated the cytotoxic capacity of PBMCs when confronted with A549 cells, while in the presence of neuroendocrine cells they not only were unable to show cytolytic activity, but also lost viability. Neuroendocrine differentiation seems to mount less of an immune response when injected in mice, which may contribute to the poor prognosis of cancer patients affected by this pathology.<\/jats:p>","DOI":"10.3390\/ijms24020990","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T03:12:15Z","timestamp":1672888335000},"page":"990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroendocrine Differentiation of Lung Cancer Cells Impairs the Activation of Antitumor Cytotoxic Responses in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Ricardo","family":"Fosado","sequence":"first","affiliation":[{"name":"Posgrado en Ciencias Qu\u00edmico-Biol\u00f3gicas, Facultad de Qu\u00edmica, Universidad Aut\u00f3noma de Quer\u00e9taro, Cerro de las Campanas S\/N, Quer\u00e9taro 76010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jazm\u00edn E.","family":"Soto-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Posgrado en Ciencias Qu\u00edmico-Biol\u00f3gicas, Facultad de Qu\u00edmica, Universidad Aut\u00f3noma de Quer\u00e9taro, Cerro de las Campanas S\/N, Quer\u00e9taro 76010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Elvira","family":"N\u00fa\u00f1ez-Anita","sequence":"additional","affiliation":[{"name":"Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Tar\u00edmbaro 58893, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-8304","authenticated-orcid":false,"given":"Carmen","family":"Aceves","sequence":"additional","affiliation":[{"name":"Instituto de Neurobiolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico-Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6266-3457","authenticated-orcid":false,"given":"Laura C.","family":"Berumen","sequence":"additional","affiliation":[{"name":"Posgrado en Ciencias Qu\u00edmico-Biol\u00f3gicas, Facultad de Qu\u00edmica, Universidad Aut\u00f3noma de Quer\u00e9taro, Cerro de las Campanas S\/N, Quer\u00e9taro 76010, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irasema","family":"Mendieta","sequence":"additional","affiliation":[{"name":"Posgrado en Ciencias Qu\u00edmico-Biol\u00f3gicas, Facultad de Qu\u00edmica, Universidad Aut\u00f3noma de Quer\u00e9taro, Cerro de las Campanas S\/N, Quer\u00e9taro 76010, Mexico"},{"name":"Instituto de Neurobiolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico-Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla, Quer\u00e9taro 76230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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