{"doi":"10.1038/s41392-020-00449-4","title":"Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy","abstract":"<jats:title>Abstract</jats:title><jats:p>Despite great success in cancer immunotherapy, immune checkpoint-targeting drugs are not the most popular weapon in the armory of cancer therapy. Accumulating evidence suggests that the tumor immune microenvironment plays a critical role in anti-cancer immunity, which may result in immune checkpoint blockade therapy being ineffective, in addition to other novel immunotherapies in cancer patients. In the present review, we discuss the deficiencies of current cancer immunotherapies. More importantly, we highlight the critical role of tumor immune microenvironment regulators in tumor immune surveillance, immunological evasion, and the potential for their further translation into clinical practice. Based on their general targetability in clinical therapy, we believe that tumor immune microenvironment regulators are promising cancer immunotherapeutic targets. Targeting the tumor immune microenvironment, alone or in combination with immune checkpoint-targeting drugs, might benefit cancer patients in the future.</jats:p>","journal":"Signal Transduction and Targeted Therapy","year":2021,"id":31549,"datarank":8.289987484356667,"base_score":6.403574197934815,"endowment":6.403574197934815,"self_citation_contribution":0.9605361296902224,"citation_network_contribution":7.329451354666444,"self_endowment_contribution":0.9605361296902224,"citer_contribution":7.329451354666444,"corpus_percentile":null,"corpus_rank":null,"citation_count":603,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":25,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":18064,"name":"Xing Huang","orcid":"0000-0002-6055-5089","position":1,"is_corresponding":false},{"id":168844,"name":"Gang Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":168845,"name":"Zhengtao Hong","orcid":null,"position":3,"is_corresponding":false},{"id":168846,"name":"Xueli Bai","orcid":null,"position":4,"is_corresponding":false},{"id":132195,"name":"Tingbo Liang","orcid":null,"position":5,"is_corresponding":false},{"id":3414,"name":"Tianyu Tang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":6.403574197934815,"endowment":6.403574197934815,"datacite_reuse_total":25,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33608497","pmcid":"PMC7896069","openalex_id":"https://openalex.org/W3129646946","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"31970696","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81502975","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81871925","title":null},{"funder_name":"China Postdoctoral Science Foundation","grant_id":"","title":null},{"funder_name":"Key Research and Development Program of Zhejiang Province","grant_id":"","title":null},{"funder_name":"National Key Research and Development Program","grant_id":"","title":null}],"total_grants":6,"fwci":32.8981,"citation_percentile":0.99861097,"influential_citations":5,"citation_trend":[{"year":2021,"count":27},{"year":2022,"count":96},{"year":2023,"count":80},{"year":2024,"count":153},{"year":2025,"count":183},{"year":2026,"count":63}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s41392-020-00449-4.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/s41392-020-00449-4.pdf","host_type":"GOLD"},{"url":"https://www.nature.com/articles/s41392-020-00449-4.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s41392-020-00449-4","host_type":"publisher"},{"url":"https://doi.org/10.1038/s41392-020-00449-4","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33608497","host_type":"repository"},{"url":"https://doaj.org/article/9a3f4a4d417241aa911f5ae2e7d41cc0","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7896069","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7896069","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7896069?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cancer Immunotherapy and Biomarkers","Immune Cell Function and Interaction","Immune cells in cancer","Medicine","Biology","Humans","Immune Checkpoint Inhibitors","Immunotherapy","Neoplasms","Tumor Microenvironment"],"mesh_terms":["Immune Checkpoint Inhibitors","Humans","Immunotherapy","Neoplasms","Tumor Microenvironment"],"keywords":["Tumor microenvironment","Immune system","Immunotherapy","Immune checkpoint","Cancer immunotherapy","Cancer","Immunology","Medicine","Cancer research","Internal medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.16986925.v1","title":"Additional file 1 of Hiding in the dark: pan-cancer characterization of expression and clinical relevance of CD40 to immune checkpoint blockade therapy","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.16986925","title":"Additional file 1 of Hiding in the dark: pan-cancer characterization of expression and clinical relevance of CD40 to immune checkpoint blockade therapy","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19606759.v1","title":"Additional file 1 of DualGCN: a dual graph convolutional network model to predict cancer drug response","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19606759","title":"Additional file 1 of DualGCN: a dual graph convolutional network model to predict cancer drug response","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19915407.v1","title":"Additional file 1 of Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19915407","title":"Additional file 1 of Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19915410.v1","title":"Additional file 2 of Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19915410","title":"Additional file 2 of Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19915413.v1","title":"Additional file 3 of Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19915413","title":"Additional file 3 of Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501909.v1","title":"Additional file 1 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501909","title":"Additional file 1 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501912.v1","title":"Additional file 2 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501912","title":"Additional file 2 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501915.v1","title":"Additional file 3 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501915","title":"Additional file 3 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501918.v1","title":"Additional file 4 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501918","title":"Additional file 4 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501921.v1","title":"Additional file 5 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.20501921","title":"Additional file 5 of Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.21455983.v1","title":"Additional file 2 of High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.21455983","title":"Additional file 2 of High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.21455986.v1","title":"Additional file 3 of High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.21455986","title":"Additional file 3 of High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.21455989.v1","title":"Additional file 4 of High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T07:33:33.619666Z","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,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}