{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:58:41Z","timestamp":1783403921560,"version":"3.54.6"},"reference-count":25,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shenzhen Foundation of Science and Technology","award":["JCYJ20210324111013036"],"award-info":[{"award-number":["JCYJ20210324111013036"]}]},{"name":"Shenzhen Foundation of Science and Technology","award":["JCYJ20190809160001751"],"award-info":[{"award-number":["JCYJ20190809160001751"]}]},{"name":"Funds for Scholar of Shenzhen Baoan People\u2019s Hospital","award":["BAYYZDXK001"],"award-info":[{"award-number":["BAYYZDXK001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>Tumor-infiltrating lymphocytes (TILs) exist in various malignancies, and have been viewed as a promising biomarker to predict the efficacy and outcome of treatment. However, the marked inter- and intra-tumor heterogeneity of TILs has resulted in some confusion regarding their impact on the prognosis of colorectal cancer (CRC).<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Methods<\/jats:title>\n               <jats:p>In this study, 78 CRC patients were enrolled and the CD3+ and CD8+ TILs densities at the tumor center (TC), the invasive margin (IM) and the tumor stroma (TS) were assessed by immunohistochemical staining. Their associations with clinicopathological features and progression free survival (PFS) were analyzed to evaluate the predictive and prognostic values of TILs.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>TILs were mainly distributed along the invasive margin. High density of TILs in tumor center and invasive margin was associated with smaller tumor size (CD3+TILs<jats:sup>IM<\/jats:sup>), reduced tumor invasion (CD3+TILs<jats:sup>IM<\/jats:sup>), absence of lymph node metastasis (CD3+TILs<jats:sup>IM<\/jats:sup> and CD8+TILs<jats:sup>TC<\/jats:sup>), earlier stage (CD3+TILs<jats:sup>IM<\/jats:sup> and CD8+TILs<jats:sup>IM<\/jats:sup>), and lower tumor grade (CD3+TILs<jats:sup>IM<\/jats:sup> and CD8+TILs<jats:sup>TC<\/jats:sup>). However, stromal TILs were not associated with any clinicopathological features. Kaplan\u2013Meier survival analysis revealed that high densities of TILs always correlated with prolonged patient survival. The pathological N stage, CD3+ TILs<jats:sup>IM<\/jats:sup> and CD8+ TILs<jats:sup>TC<\/jats:sup> were found to be independent prognostic indicators. Additionally, early-stage CRC patients who developed recurrence after surgery, showed a higher CD3+\/CD8+ TILs ratio in invasive margin. In the present study, it was clarified that CD3+ and CD8+ TILs were heterogeneously distributed in tumor tissues of CRC. The increase in intratumoral and peritumoral TILs had been shown to be strongly predictive of improved clinical outcome. More importantly, the immune signatures enabled to stratify early-stage CRC patients with high risk of recurrence, highlighting the prognostic power of TILs.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.16747","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T08:16:04Z","timestamp":1704788164000},"page":"e16747","source":"Crossref","is-referenced-by-count":3,"title":["Clinical impact of heterogeneously distributed tumor-infiltrating lymphocytes on the prognosis of colorectal cancer"],"prefix":"10.7717","volume":"12","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Shenzhen People\u2019s Hospital of Baoan District, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Long","sequence":"additional","affiliation":[{"name":"Xinyi People\u2019s Hospital, Maoming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyuan","family":"Su","sequence":"additional","affiliation":[{"name":"Shenzhen People\u2019s Hospital of Baoan District, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen People\u2019s Hospital of Baoan District, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintao","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Baoan Traditional Chinese Medicine Hospital Group, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"10.7717\/peerj.16747\/ref-1","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1200\/JCO.21.02538","article-title":"Adjuvant therapy for stage II colon cancer: ASCO guideline update","volume":"40","author":"Baxter","year":"2022","journal-title":"Journal of Clinical Oncology"},{"key":"10.7717\/peerj.16747\/ref-2","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1016\/S0140-6736(13)61649-9","article-title":"Colorectal cancer","volume":"383","author":"Brenner","year":"2014","journal-title":"Lancet"},{"key":"10.7717\/peerj.16747\/ref-3","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1038\/sj.bjc.6602201","article-title":"Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis","volume":"91","author":"Chiba","year":"2004","journal-title":"British Journal of Cancer"},{"key":"10.7717\/peerj.16747\/ref-4","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1002\/ijc.24989","article-title":"High frequency of tumor-infiltrating FOXP3(+) regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients","volume":"126","author":"Frey","year":"2010","journal-title":"International Journal of Cancer"},{"key":"10.7717\/peerj.16747\/ref-5","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nrc3245","article-title":"The immune contexture in human tumours: impact on clinical outcome","volume":"12","author":"Fridman","year":"2012","journal-title":"Nature Reviews. 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