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CD45RO seems to be a reliable indicator for predicting prognosis and disease outcome, along with CD3 and CD8 markers. LAG-3 is another important marker that overexpresses on TILs in a variety of cancers and is associated with disease prognosis; however, its prognostic impact is controversial. Hence, in the present study, we aimed to investigate the presence of CD45RO\u2009+\u2009, LAG3\u2009+\u2009, CD3\u2009+\u2009, and CD8\u2009+\u2009lymphocytes in CRC tumor tissues and their association with clinicopathological parameters of the disease as well as patients' survival, according to primary tumor locations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Expression of CD45RO, LAG3, CD3, and CD8 was immunohistochemically assessed in tissue sections of 136 patients with CRC. The percentages of TILs expressing these markers were then separately determined in both invasive margin (IM) and center of tumor (CT). Their associations with clinicopathological factors and patients\u2019 survival were analyzed in the entire cohort and the subgroups of patients with right- and left- rectum tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Based on our observation, CD45RO\u2009+\u2009and CD3\u2009+\u2009cells were the most frequent infiltrated lymphocytes in both CT and IM regions of colon tumor tissue. Whilst, LAG3\u2009+\u2009lymphocytes were the least frequent subset in both areas. Statistical analysis indicated that the frequency of CD45RO\u2009+\u2009TILs was positively associated with advanced TNM stages (III\/IV), in the entire cohort and right-sided tumors (P\u2009&lt;\u20090.05). LAG3\u2009+\u2009TILs in IM were also increased in tumor tissues with higher T-stages in the entire cohort (P\u2009=\u20090.027). In univariate analysis, high score of CD45RO\u2009+\u2009TILs in IM was associated with better overall survival in the entire cohort. High score of CD8\u2009+\u2009and CD45RO\u2009+\u2009lymphocytes in IM were also associated with improved survival in patients with right-sided tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings generally suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD45RO and LAG3 depends on the primary tumor sides. Our results collectively demonstrated that infiltration of CD45RO\u2009+\u2009lymphocytes in IM could be an independent prognostic factor in a site-dependent manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12935-023-02864-3","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T03:08:30Z","timestamp":1675998510000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Clinicopathological significance and prognostic role of LAG3\u2009+\u2009tumor-infiltrating lymphocytes in colorectal cancer; relationship with sidedness"],"prefix":"10.1186","volume":"23","author":[{"given":"Shirin","family":"Tavana","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Mokhtari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Hossein","family":"Sanei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Heidari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir-Reza","family":"Dehghanian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Faghih","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzieh","family":"Rezaei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"issue":"4","key":"2864_CR1","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","volume":"66","author":"M Arnold","year":"2017","unstructured":"Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. 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