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Immunotherapy treatments like PD-L1 blockade have been used to inhibit the PD-L1 legend, which boosts the activity of cytotoxic T lymphocytes. Recently, studies suggest that some probiotics could potentially enhance the effectiveness of immunotherapy treatments for cancer patients. We found that in Caco-2 and HT-29 cells, the live <jats:italic>Leuconostoc mesenteroides<\/jats:italic> treatment resulted an increase in the PD-L1 expression and this treatment stimulated interferon-gamma (IFN-\u03b3) production in Jurkat T-cells. Due to the well-established ability of IFN-\u03b3 to enhance PD-L1 expression, the combination of IFN-\u03b3 and <jats:italic>L. mesenteroides<\/jats:italic> was used in colon cancer cell lines and a resulting remarkable increase of over tenfold in PD-L1 expression was obtained. Interestingly, when <jats:italic>L. mesenteroides<\/jats:italic> and IFN-\u03b3 are present, the blockage of PD-L1 using PD-L1 antibodies not only improved the viability of Jurkat T-cells but also significantly boosted the levels of IFN-\u03b3 and IL-2, the T-cells activation marker cytokines. In addition to upregulating PD-L1, <jats:italic>L. mesenteroides<\/jats:italic> also activated Toll-like receptors (TLRs) and NOD-like receptors (NODs) pathways, specifically through TLR2 and NOD2, while also exerting a suppressive effect on autophagy in colon cancer cell lines. In conclusion, our findings demonstrate a significant upregulation of PD-L1 expression in colon cancer cells upon co-culturing with <jats:italic>L. mesenteroides<\/jats:italic>. Moreover, the presence of PD-L1 antibodies during co-culturing activates Jurkat T cells. The observed enhancement in PD-L1 expression may be attributed to the inhibition of the Autophagy pathway or activation of the hippo pathway.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract text<\/jats:title>\n                <jats:p>The administration of Live <jats:italic>Lactobacillus mesenteroides<\/jats:italic> on colon cancer cells leads to the elevation of PD-L1, with a further increase observed in the presence of IFN-\u03b3. Co-cultivation of Live <jats:italic>L. mesenteroides<\/jats:italic> with colon cancer cells in conjunction with anti-PD-L1 blockade antibody results in the enhanced viability of T cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Key Points<\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>Co-culturing <jats:italic>L. mesenteroides<\/jats:italic> increases PD-L1 gene and protein transaction in colon cancer.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p><jats:italic>L. mesenteroides<\/jats:italic> existing enhances T cells viability and activity.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>GPCR41\/42 is a possible link between <jats:italic>L. mesenteroides<\/jats:italic>, YAP-1 and PD-L1.<\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11274-024-04018-7","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T02:01:41Z","timestamp":1715911301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Upregulation of Immune checkpoint PD-L1 in Colon cancer cell lines and activation of T cells by Leuconostoc mesenteroides"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5873-2085","authenticated-orcid":false,"given":"Safaa","family":"Altves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-6159","authenticated-orcid":false,"given":"Ebru","family":"Guclu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8606-4424","authenticated-orcid":false,"given":"Esra","family":"Yetisgin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6254-3516","authenticated-orcid":false,"given":"Kivanc","family":"Bilecen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2564-7807","authenticated-orcid":false,"given":"Hasibe","family":"Vural","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"4018_CR1","doi-asserted-by":"publisher","unstructured":"Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB (2008) Cancer is a preventable disease that requires major lifestyle changes. 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Ebru Guclu declares that she has no conflict of interest. Esra Yetisgin declares that she has no conflict of interest. Kivanc Bilecen declares that he has no conflict of interest. Hasibe Vural declares that she has no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This research is supported by Necmettin Erbakan University, Scientific Research Projects (#201418012) as a part of Safaa Altves\u2019s Ph.D. dissertation. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"204"}}