{"doi":"10.1080/13543784.2022.2152323","title":"Next-generation immunotherapy for solid tumors: combination immunotherapy with crosstalk blockade of TGFβ and PD-1/PD-L1","abstract":"INTRODUCTION: In solid tumor immunotherapy, less than 20% of patients respond to anti-programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) agents. The role of transforming growth factor β (TGFβ) in diverse immunity is well-established; however, systemic blockade of TGFβ is associated with toxicity. Accumulating evidence suggests the role of crosstalk between TGFβ and PD-1/PD-L1 pathways. AREAS COVERED: We focus on TGFβ and PD-1/PD-L1 signaling pathway crosstalk and the determinant role of TGFβ in the resistance of immune checkpoint blockade. We provide the rationale for combination anti-TGFβ and anti-PD-1/PD-L1 therapies for solid tumors and discuss the current status of dual blockade therapy in preclinical and clinical studies. EXPERT OPINION: The heterogeneity of tumor microenvironment across solid tumors complicates patient selection, treatment regimens, and response and toxicity assessment for investigation of dual blockade agents. However, clinical knowledge from single-agent studies provides infrastructure to translate dual blockade therapies. Dual TGFβ and PD-1/PD-L1 blockade results in enhanced T-cell infiltration into tumors, a primary requisite for successful immunotherapy. A bifunctional fusion protein specifically targets TGFβ in the tumor microenvironment, avoiding systemic toxicity, and prevents interaction of PD-1+ cytotoxic cells with PD-L1+ tumor cells.","journal":"Expert Opinion on Investigational Drugs","year":2022,"id":278314,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":854450,"name":"Zhaohua Hou","orcid":"0000-0003-3093-0279","position":1,"is_corresponding":false},{"id":666435,"name":"Rebecca Y. Bellis","orcid":"0000-0002-4219-0733","position":2,"is_corresponding":false},{"id":666434,"name":"Jasmeen Saini","orcid":"0000-0003-0601-8271","position":3,"is_corresponding":false},{"id":854451,"name":"Alfredo Amador-Molina","orcid":"0009-0009-6406-3565","position":4,"is_corresponding":false},{"id":227919,"name":"Prasad S. Adusumilli","orcid":"0000-0002-1699-2046","position":5,"is_corresponding":false},{"id":504096,"name":"Yuquan Xiong","orcid":null,"position":6,"is_corresponding":false},{"id":692615,"name":"Hue Tu Quach","orcid":"0000-0001-5571-1908","position":0,"is_corresponding":true}],"reference_count":136,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:28:43.133347Z","pmid":"36448335","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":[]}