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TICs\/CSCs are developed from their cells-of-origin. In breast, prostate, and ovarian cancers, progenitor cells for mammary alveolar cells, prostate luminal (secretory) cells, and fallopian tube secretory cells are the preferred cellular origins for their corresponding cancer types. These luminal progenitors (LPs) express common innate immune program (e.g., Toll-like receptor (TLR) signaling)-related genes. Microbes such as bacteria are now found in breast, prostate, and fallopian tube tissues and their corresponding cancer types, raising the possibility that their LPs may sense the presence of microbes and trigger their innate immune\/TLR pathways, leading to an inflammatory microenvironment. Crosstalk between immune cells (e.g., macrophages) and affected epithelial cells (e.g., LPs) may eventually contribute to formation of TICs\/CSCs from their corresponding LPs, in part via STAT3 and\/or NF\u03baB pathways. As such, TICs\/CSCs can inherit expression of innate-immunity\/TLR-pathway-related genes from their cells-of-origin; the innate immune program may also represent their unique vulnerability, which can be explored therapeutically (e.g., by enhancing immunotherapy via augmenting TLR signaling).<\/jats:p>","DOI":"10.3390\/cancers15030757","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T02:30:38Z","timestamp":1674786638000},"page":"757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Innate Immune Program in Formation of Tumor-Initiating Cells from Cells-of-Origin of Breast, Prostate, and Ovarian Cancers"],"prefix":"10.3390","volume":"15","author":[{"given":"Sen","family":"Han","sequence":"first","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-0885","authenticated-orcid":false,"given":"Zhe","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/embr.201338254","article-title":"Dedifferentiation and reprogramming: Origins of cancer stem cells","volume":"15","author":"Verma","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nm0797-730","article-title":"Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell","volume":"3","author":"Bonnet","year":"1997","journal-title":"Nat. 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