{"doi":"10.3389/fonc.2020.00968","title":"Akt Inhibition Is Associated With Favorable Immune Profile Changes Within the Tumor Microenvironment of Hormone Receptor Positive, HER2 Negative Breast Cancer","abstract":"Background: The PI3K/Akt/mTOR pathway in part impacts tumorigenesis through modulation of host immune activity. To assess the effects of Akt inhibition on the tumor micro-environment (TME), we analyzed tumor tissue from patients with operable hormone receptor positive, HER2 negative breast cancer (BC) treated on a presurgical trial with the Akt inhibitor MK-2206. Methods: Quantitative multiplex immunofluorescence (qmIF) was performed using CD3, CD8, CD4, FOXP3, CD68, and pancytokeratin on biopsy and surgical specimens of MK-2206 and untreated, control patients. nanoString was performed on surgical specimens to assess mRNA expression from MK-2206-treated vs. control patients. Results: Increased CD3+CD8+ density was observed in post vs. pre-treatment tissue in the MK-2206-treated vs. control patients (87% vs. 0.2%, p <0.05). MK-2206 was associated with greater expression of interferon signaling genes (e.g. IFI6, p<0.05) and lower expression of myeloid genes (CD163, p<0.05) on differential expression and gene set enrichment analyses. Lower expression of anti-apoptotic genes (BAX) and greater expression of pro-apoptotic genes (BAD) were associated with MK-2206 (p<0.05). Conclusion: Akt inhibition in operable BC was associated with a favorable immune profile in the TME, including increased CD3+CD8+ density and greater expression of interferon genes. Additional studies are warranted, as this may provide rationale for combining Akt inhibition with immunotherapy.","journal":"Frontiers in Oncology","year":2020,"id":101580,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":409101,"name":"Robyn D. Gartrell","orcid":"0000-0003-3287-4223","position":1,"is_corresponding":false},{"id":497237,"name":"Margueritta El Asmar","orcid":"0000-0002-7613-1782","position":2,"is_corresponding":false},{"id":497238,"name":"Shuobo Boboila","orcid":"0009-0005-6788-2065","position":3,"is_corresponding":false},{"id":157,"name":"Thomas D. Hart","orcid":null,"position":4,"is_corresponding":false},{"id":497239,"name":"Yan Lu","orcid":"0000-0001-8153-7149","position":5,"is_corresponding":false},{"id":497240,"name":"Qingfei Pan","orcid":"0000-0003-0243-6898","position":6,"is_corresponding":false},{"id":55257,"name":"Jiyang Yu","orcid":"0000-0003-1244-4429","position":7,"is_corresponding":false},{"id":69823,"name":"Hanina Hibshoosh","orcid":"0000-0001-9688-4514","position":8,"is_corresponding":false},{"id":371033,"name":"Hua Guo","orcid":"0000-0001-9901-053X","position":9,"is_corresponding":false},{"id":276781,"name":"Eleni Andreopoulou","orcid":null,"position":10,"is_corresponding":false},{"id":380086,"name":"Lisa Wiechmann","orcid":null,"position":11,"is_corresponding":false},{"id":497241,"name":"Katherine D. Crew","orcid":"0000-0002-9637-2962","position":12,"is_corresponding":false},{"id":245492,"name":"Joseph A. Sparano","orcid":"0000-0002-9031-2010","position":13,"is_corresponding":false},{"id":107125,"name":"Dawn L. Hershman","orcid":"0000-0001-8807-153X","position":14,"is_corresponding":false},{"id":497242,"name":"Eileen P. Connolly","orcid":"0000-0001-6558-1932","position":15,"is_corresponding":false},{"id":409107,"name":"Yvonne M. Saenger","orcid":"0000-0001-7074-2681","position":16,"is_corresponding":false},{"id":260392,"name":"Kevin Kalinsky","orcid":"0000-0002-3113-7902","position":17,"is_corresponding":false},{"id":409105,"name":"Douglas K. Marks","orcid":"0000-0002-3690-7101","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T22:40:22.678835Z","pmid":"32612958","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":[]}