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dc.contributor.authorRedman, Jason M.
dc.contributor.authorFriedman, Jay
dc.contributor.authorRobbins, Yvette
dc.contributor.authorSievers, Cem
dc.contributor.authorYang, Xinping
dc.contributor.authorLassoued, Wiem
dc.contributor.authorSinkoe, Andrew
dc.contributor.authorPapanicolau-Sengos, Antonios
dc.contributor.authorLee, Chyi Chia
dc.contributor.authorMarte, Jennifer L.
dc.contributor.authorTurkbey, Evrim
dc.contributor.authorMydlarz, Wojtek
dc.contributor.authorJoshi, Arjun
dc.contributor.authorLondon, Nyall R.
dc.contributor.authorPierce, Matthew
dc.contributor.authorTaylor, Rodney
dc.contributor.authorHong, Steven
dc.contributor.authorNguyen, Andy
dc.contributor.authorSoon-Shiong, Patrick
dc.contributor.authorSchlom, Jeffrey
dc.contributor.authorGulley, James L.
dc.contributor.authorAllen, Clint T.
dc.date.accessioned2022-10-05T16:28:08Z
dc.date.available2022-10-05T16:28:08Z
dc.date.issued2022-09-15
dc.identifier.urihttp://hdl.handle.net/10713/19911
dc.description.abstractBackground. Head and neck squamous cell carcinoma not associated with HPV (HPV-unrelated HNSCC) is associated with a high rate of recurrence and poor survival. Methods. We conducted a clinical trial in 14 patients with newly diagnosed HPV-unrelated HNSCC to evaluate the safety and efficacy of neoadjuvant bintrafusp alfa, a bifunctional fusion protein that blocks programmed death ligand 1 (PD-L1) and neutralizes TGF-β. Results. Bintrafusp alfa was well tolerated, and no treatment-associated surgical delays or complications occurred. Objective pathologic responses (PRs) were observed, and 12 of the 14 (86%) patients were alive and disease free at 1 year. Alterations in Treg infiltration and spatial distribution relative to proliferating CD8+ T cells indicated a reversal of Treg immunosuppression in the primary tumor. Detection of neoepitope-specific tumor T cell responses, but not virus-specific responses, correlated with the development of a PR. Detection of neoepitope-specific responses and PRs in tumors was not correlated with genomic features or tumor antigenicity but was associated with reduced pretreatment myeloid cell tumor infiltration. These results indicate that dual PD-L1 and TGF-β blockade can safely enhance tumor antigen-specific immunity and highlight the feasibility of multimechanism neoadjuvant immunotherapy for patients with HPV-unrelated HNSCC. Conclusion. Our studies provide insight into the ability of neoadjuvant immunotherapy to induce polyclonal neoadjuvant- specific T cell responses in tumors and suggest that features of the tumor microenvironment, such as myeloid cell infiltration, may be a major determinant of enhanced antitumor immunity following such treatment.en_US
dc.description.urihttps://doi.org/10.1172/JCI161400en_US
dc.language.isoen_USen_US
dc.relation.ispartofThe Journal of clinical investigationen_US
dc.subjectClinical Trialsen_US
dc.subjectImmunologyen_US
dc.subjectImmunotherapyen_US
dc.titleEnhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-β blockade in HPV-unrelated head and neck canceren_US
dc.typeArticleen_US
dc.identifier.doi10.1172/JCI161400
dc.source.journaltitleThe Journal of clinical investigation
dc.source.volume132
dc.source.issue18


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