{"doi":"10.1371/journal.pone.0297325","title":"Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer","abstract":"BACKGROUND: Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins. METHODS: Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples. RESULTS: Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC. CONCLUSION: In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.","journal":"PLoS ONE","year":2024,"id":459191,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":400008,"name":"Kelly M. Herremans","orcid":"0000-0002-0454-0931","position":1,"is_corresponding":false},{"id":267421,"name":"Patrick W. Underwood","orcid":"0000-0002-8267-8979","position":2,"is_corresponding":false},{"id":648040,"name":"Ashwin Akki","orcid":"0000-0001-5217-7412","position":3,"is_corresponding":false},{"id":400006,"name":"Andrea N. Riner","orcid":"0000-0003-2088-5400","position":4,"is_corresponding":false},{"id":267423,"name":"José G. Treviño","orcid":"0000-0002-0265-8151","position":5,"is_corresponding":false},{"id":374590,"name":"Song Han","orcid":"0000-0002-6542-335X","position":6,"is_corresponding":false},{"id":374591,"name":"Steven J. Hughes","orcid":"0000-0002-5688-6942","position":7,"is_corresponding":false},{"id":901644,"name":"Gerik W. Tushoski-Alemán","orcid":"0000-0002-8191-4044","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:03:55.280882Z","pmid":"38346068","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":[]}