{"doi":"10.1111/cas.13542","title":"Significance of tumor‐infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer","abstract":"<jats:p>Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor‐infiltrating lymphocytes (<jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s before and after neoadjuvant treatment and the change in the density of those <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s. Sixty‐four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content> subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post‐treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s in pretreatment biopsy samples was associated with a poor response, and a low density of <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s in post‐treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s in post‐treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte‐mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.</jats:p>","journal":"Cancer Science","year":2018,"id":597276,"datarank":0.7193685818395114,"base_score":4.795790545596741,"endowment":4.795790545596741,"self_citation_contribution":0.7193685818395114,"citation_network_contribution":0.0,"self_endowment_contribution":0.7193685818395114,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":120,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1530128,"name":"Masatsune Shibutani","orcid":"0000-0002-2164-7394","position":1,"is_corresponding":false},{"id":172316,"name":"Kiyoshi Maeda","orcid":null,"position":2,"is_corresponding":false},{"id":1530129,"name":"Hisashi Nagahara","orcid":null,"position":3,"is_corresponding":false},{"id":1530130,"name":"Tatsunari Fukuoka","orcid":null,"position":4,"is_corresponding":false},{"id":1530131,"name":"Shigetomi Nakao","orcid":null,"position":5,"is_corresponding":false},{"id":1530132,"name":"Kosei Hirakawa","orcid":null,"position":6,"is_corresponding":false},{"id":269384,"name":"Masaichi Ohira","orcid":null,"position":7,"is_corresponding":false},{"id":1530127,"name":"Shinji Matsutani","orcid":"0000-0001-5340-6862","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Significance of tumor‐infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer","abstract":"<jats:p>Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor‐infiltrating lymphocytes (<jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s before and after neoadjuvant treatment and the change in the density of those <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s. Sixty‐four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content> subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post‐treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s in pretreatment biopsy samples was associated with a poor response, and a low density of <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s in post‐treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of <jats:styled-content style=\"fixed-case\">CD</jats:styled-content>8<jats:sup>+</jats:sup> <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s in post‐treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte‐mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of <jats:styled-content style=\"fixed-case\">TIL</jats:styled-content>s in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.</jats:p>","is_dataset_classified":null,"base_score":4.795790545596741,"endowment":4.795790545596741,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29464828","pmcid":"PMC5891199","openalex_id":"https://openalex.org/W2792791488","authors":[],"funders":[],"total_grants":0,"fwci":5.0157,"citation_percentile":0.97114608,"influential_citations":0,"citation_trend":[{"year":2018,"count":3},{"year":2019,"count":8},{"year":2020,"count":27},{"year":2021,"count":23},{"year":2022,"count":14},{"year":2023,"count":23},{"year":2024,"count":10},{"year":2025,"count":10},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cas.13542","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cas.13542","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcas.13542","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.13542","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.13542","host_type":"publisher"},{"url":"https://doi.org/10.1111/cas.13542","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29464828","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC5891199","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5891199","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5891199","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5891199?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer Immunotherapy and Biomarkers","Colorectal Cancer Surgical Treatments","Colorectal and Anal Carcinomas","Adult","Aged","Aged, 80 and over","Biopsy","CD8-Positive T-Lymphocytes","Chemoradiotherapy","Female","Humans","Lymphocytes, Tumor-Infiltrating","Male","Middle Aged","Neoadjuvant Therapy","Rectal Neoplasms"],"mesh_terms":["Adult","Aged","Aged, 80 and over","Biopsy","Female","Humans","Male","Middle Aged","Rectal Neoplasms","Lymphocytes, Tumor-Infiltrating","CD8-Positive T-Lymphocytes","Neoadjuvant Therapy","Chemoradiotherapy"],"keywords":["Medicine","Colorectal cancer","Neoadjuvant therapy","Tumor-infiltrating lymphocytes","Chemoradiotherapy","Biopsy","Radiation therapy","Oncology","Internal medicine","Immune system","Chemotherapy","Immunohistochemistry","Cancer","Pathology","Immunotherapy","Breast cancer","Immunology","Rectal cancer","Predictive Marker","Tumor-infiltrating Lymphocyte"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.26731246.v1","title":"Additional file 1 of Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26731246","title":"Additional file 1 of Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T12:49:13.541158Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}