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In hepatocellular carcinoma (HCC), the presence of TLSs was closely associated with immunotherapy response and prognostic outcomes. However, TLSs exhibit pronounced spatial heterogeneity within tumors and biopsy, being invasive and prone to sampling bias, may cause inaccurate assessments. Multi-parametric imaging techniques based on computed tomography (CT)\/magnetic resonance imaging (MRI)CT\/MRICT\/MRI with the aid of artificial intelligence (AI) algorithms could effectively integrate anatomical structures with functional metabolic information, quantifying and visualizing key pathological molecular features of tumor treatment response across multiple dimensions. This review summarizes the biological characteristics and clinical significance of TLSs in hepatocellular carcinoma. Furthermore, it focuses on the latest advances in non-invasive TLS assessment using multi-parametric imaging techniques, integrating these technologies with large-scale artificial intelligence models to explore their application value in prognosis prediction and immunotherapy benefit evaluation.<\/jats:p>","DOI":"10.3390\/cancers18182978","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:16:48Z","timestamp":1789460208000},"page":"2978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Invasive Assessment of Tertiary Lymphoid Structure in Hepatocellular Carcinoma Based on Multi-Parameter Imaging: From Tumor Immunobiology to Immunotherapy Benefit Prediction"],"prefix":"10.3390","volume":"18","author":[{"given":"Dan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ren","sequence":"additional","affiliation":[{"name":"CT Imaging Research Center, GE Healthcare China, Beijing 100176, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-2101","authenticated-orcid":false,"given":"Bin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hehan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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