Regulatory T cell and activated natural killer cell infiltration in hepatocellular carcinoma: immune cell profiling using the CIBERSORT.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33313228", "kind": "science-record", "revision": 5, "content_hash": "sha256:1415ba3b1413b686b63038d3a70a4e0b834d3921cd9e98f44b421fe59a931971", "created_at": "2026-11-01T15:41:19Z", "updated_at": "2026-11-01T21:24:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Regulatory T cell and activated natural killer cell infiltration in hepatocellular carcinoma: immune cell profiling using the CIBERSORT.", "doi": "10.21037/atm-20-5830", "pmid": "33313228", "authors": ["Lixin Wang", "Zongguo Yang", "Yajuan Cao"], "journal": "Annals of translational medicine", "year": 2020, "abstract": "BACKGROUND: Hepatocellular carcinoma (HCC) is understood to be an immunogenic tumor caused by chronic liver disease. Emerging research has indicated close interaction between various immune cells and tumor cells. Immunophenotyping, which has shown potential predictive value for the prognosis of various human malignancies, might allow responsive and non-responsive patients to be identified based on the extent and distribution of immune cell infiltration. Several novel immunotherapeutic approaches have been trialed and have shown promising efficacy. However, the efficacy of immunotherapies in HCC is limited by several factors. This study aimed to investigate tumor-infiltrating immune cells in HCC.\nMETHODS: Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) allows immune cell profiling analysis by deconvolution of gene expression microarray data. In this study, we analyzed the proportions of immune cells in 14 paired samples of HCC tissues obtained from GSE84402 in Gene Expression Omnibus (GEO) database.\nRESULTS: In the 14 paired samples, HCC tissues showed significant infiltration by regulatory T cells (Tregs), activated natural killer (NK) cells, and M0 macrophages (P<0.001, P=0.007 and P=0.001, respectively), which were validated in CIBERSORT with the P value set at ≤0.05. In four paired samples identified from those selected by CIBERSORT, HCC tissues were found to have significant Treg and activated NK cell infiltration compared to non-tumor tissues (P=0.007 and P=0.015, respectively). Additionally, Pearson correlation analysis revealed Tregs to be positively correlated with activated NK cells (Correlation coefficient =0.41).\nCONCLUSIONS: HCC tumor tissues were markedly infiltrated by Tregs and activated NK cells, which should be considered as candidate therapeutic targets in HCC multidisciplinary treatments.", "claims": [{"id": "claim-method", "statement": "CIBERSORT was used to obtain the immune cell profile of each sample from GSE84402, with the number of permutations set at 100 (17).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33313228", "locator": "sections[4] \"CIBERSORT analysis\" paragraph 2", "quote": "CIBERSORT was used to obtain the immune cell profile of each sample from GSE84402, with the number of permutations set at 100 (17)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE84402 series comprising 14 pairs of HCC tissues and the corresponding non-cancerous tissues was obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE84402 series matrix file and platform documents (GPL570) were downloaded.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33313228", "locator": "sections[3] \"Data source\" paragraph 2", "quote": "The GSE84402 series comprising 14 pairs of HCC tissues and the corresponding non-cancerous tissues was obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/)."}, {"asset": "source:pmid:33313228", "locator": "sections[3] \"Data source\" paragraph 3", "quote": "The GSE84402 series matrix file and platform documents (GPL570) were downloaded."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33313228"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE84402"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE84402"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33313228", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm-20-5830", "sha256": "sha256:b5fce36774446894fa79c700497d2637ea8df2c3fd70c10fa1536ab46e891c17", "bytes": 16172, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/atm-20-5830", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7729330", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE84402", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE84402", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE84402", "version": null, "note": "The GSE84402 series comprising 14 pairs of HCC tissues and the corresponding non-cancerous tissues was obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE84402 series matrix file and platform documents (GPL570) were downloaded.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GSE84402 series comprising 14 pairs of HCC tissues and the corresponding non-cancerous tissues was obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE84402 series matrix file and platform documents (GPL570) were downloaded.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2233086", "GSM2233087", "GSM2233088", "GSM2233089", "GSM2233090", "GSM2233091", "GSM2233092", "GSM2233093", "GSM2233094", "GSM2233095", "GSM2233096", "GSM2233097", "GSM2233098", "GSM2233099", "GSM2233100", "GSM2233101", "GSM2233102", "GSM2233103", "GSM2233104", "GSM2233105", "GSM2233106", "GSM2233107", "GSM2233108", "GSM2233109", "GSM2233110", "GSM2233111", "GSM2233112", "GSM2233113"], "sample_count": 28, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data from human hepatocellular carcinoma tissues and the correponding non-cancerous tissues", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33313228:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7f1b65b698d7058e2be3fc5fe409d14333f95922af0acff6a94bdc22348acbc2", "bytes": 1691, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[1]#t1", "version": null, "note": "Comparison of CIBERSORT immune cell fractions between tumor and non-tumor tissues from HCC patients", "structure": {"pmcid": "PMC7729330", "section_index": 4, "section_title": "CIBERSORT analysis", "row_count": 24, "column_count": 4}, "table": {"label": "Table 1", "caption": "Comparison of CIBERSORT immune cell fractions between tumor and non-tumor tissues from HCC patients", "rows": [["Immune cell type", "CIBERSORT fraction in % of all infiltrating immune cells (mean ± SD)"], ["Tumors (n=14)", "Non-tumors (n=14)", "P value"], ["T cells CD8", "0.140±0.071", "0.192±0.073", "0.075"], ["T cells CD4 naive", "0.0±0.0", "0.0±0.0", "1.0"], ["T cells CD4 memory resting", "0.071±0.082", "0.088±0.066", "0.553"], ["T cells CD4 memory activated", "0.002±0.008", "0.0±0.001", "0.408"], ["T cells follicular helper", "0.074±0.030", "0.066±0.030", "0.545"], ["T cells regulatory (Tregs)", "0.066±0.040", "0.011±0.017", "<0.001"], ["T cells gamma delta", "0.004±0.009", "0.012±0.017", "0.109"], ["B cells naive", "0.013±0.017", "0.020±0.027", "0.454"], ["B cells memory", "0.022±0.026", "0.008±0.016", "0.133"], ["Plasma cells", "0.065±0.025", "0.061±0.022", "0.658"], ["NK cells resting", "0.008±0.016", "0.006±0.009", "0.709"], ["NK cells activated", "0.040±0.021", "0.017±0.019", "0.007"], ["Macrophages M0", "0.043±0.041", "0.0±0.003", "0.001"], ["Macrophages M1", "0.090±0.030", "0.090±0.033", "0.965"], ["Macrophages M2", "0.143±0.081", "0.169±0.054", "0.351"], ["Monocytes", "0.033±0.024", "0.056±0.034", "0.056"], ["Dendritic cells resting", "0.074±0.059", "0.043±0.024", "0.085"], ["Dendritic cells activated", "0.003±0.007", "0.0±0.0", "0.160"], ["Mast cells resting", "0.003±0.011", "0.001±0.003", "0.505"], ["Mast cells activated", "0.081±0.055", "0.125±0.144", "0.318"], ["Eosinophils", "0.0±0.0", "0.0±0.0", "1.0"], ["Neutrophils", "0.026±0.020", "0.033±0.015", "0.313"]], "row_count": 24, "column_count": 4, "numeric_cells": 68, "header_rows": 2, "locator": "section[4]/table-wrap[1]#t1"}}, {"id": "asset:table:pmid:33313228:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c316a21ca1e1c467732b5aee8b1c0d36dd150a123877fedc8bd250ea22e37670", "bytes": 1689, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[4]/table-wrap[2]#t2", "version": null, "note": "Comparison of CIBERSORT-selected immune cell fractions between tumor and non-tumor tissues from HCC patients", "structure": {"pmcid": "PMC7729330", "section_index": 4, "section_title": "CIBERSORT analysis", "row_count": 24, "column_count": 4}, "table": {"label": "Table 2", "caption": "Comparison of CIBERSORT-selected immune cell fractions between tumor and non-tumor tissues from HCC patients", "rows": [["Immune cell type", "CIBERSORT fraction in % of all infiltrating immune cells (mean ± SD)"], ["Tumors (n=8)", "Non-tumors (n=7)", "P value"], ["T cells CD8", "0.164±0.066", "0.198±0.080", "0.422"], ["T cells CD4 naive", "0.0±0.0", "0.0±0.0", "1.0"], ["T cells CD4 memory resting", "0.043±0.065", "0.058±0.047", "0.64"], ["T cells CD4 memory activated", "0.005±0.011", "0.001±0.002", "0.372"], ["T cells follicular helper", "0.069±0.033", "0.077±0.031", "0.675"], ["T cells regulatory (Tregs)", "0.052±0.035", "0.008±0.009", "0.007"], ["T cells gamma delta", "0.007±0.011", "0.020±0.019", "0.152"], ["B cells naive", "0.018±0.018", "0.023±0.030", "0.479"], ["B cells memory", "0.017±0.028", "0.0±0.001", "0.132"], ["Plasma cells", "0.069±0.031", "0.064±0.028", "0.759"], ["NK cells resting", "0.005±0.012", "0.002±0.004", "0.578"], ["NK cells activated", "0.042±0.027", "0.015±0.019", "0.05"], ["Macrophages M0", "0.047±0.049", "0.0±0.0", "0.025"], ["Macrophages M1", "0.104±0.029", "0.094±0.039", "0.605"], ["Macrophages M2", "0.126±0.053", "0.155±0.050", "0.326"], ["Monocytes", "0.031±0.028", "0.055±0.033", "0.184"], ["Dendritic cells resting", "0.082±0.065", "0.035±0.019", "0.09"], ["Dendritic cells activated", "0.003±0.006", "0.0±0.001", "0.31"], ["Mast cells resting", "0.0±0.0", "0.002±0.004", "0.369"], ["Mast cells activated", "0.093±0.059", "0.154±0.183", "0.444"], ["Eosinophils", "0.0±0.0", "0.0±0.0", "1.0"], ["Neutrophils", "0.021±0.010", "0.032±0.012", "0.097"]], "row_count": 24, "column_count": 4, "numeric_cells": 68, "header_rows": 2, "locator": "section[4]/table-wrap[2]#t2"}}], "gaps": ["asset:data:geo:GSE84402 not downloaded", "asset:data:geo:GSE84402 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "correlation_analysis", 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE84402"], "resolved_accessions": ["GSE84402"], "statements": ["The GSE84402 series comprising 14 pairs of HCC tissues and the corresponding non-cancerous tissues was obtained from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE84402 series matrix file and platform documents (GPL570) were downloaded."], "basis": "The paper names GSE84402 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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