Sara Isabel Pai, MD, PhD
ProfessorCards
About
Research
Publications
2026
The Patient Perspective of Living With Recurrent Respiratory Papillomatosis
Pai S, Ochieng W, Hedlund N, Martino A, Chohan N, Pawlak M, Morais E, McClellan K. The Patient Perspective of Living With Recurrent Respiratory Papillomatosis. The Laryngoscope 2026 PMID: 41718509, DOI: 10.1002/lary.70412.Peer-Reviewed Original ResearchRecurrent respiratory papillomatosisHuman papillomavirusDisease burdenMiles round tripRespiratory papillomatosisMental health assistanceFeelings of isolationResponses to questionnaireSpecialty careHuman papillomavirus infectionPatient perspectiveRetrospective descriptive analysisPsychosocial burdenHuman papillomavirus vaccineHealth assistancePatient RegistryFamily incomeAO-RRPDescriptive analysisJO-RRPInterquartile rangeCategorical variablesStudy objectiveCarePublic awarenessCCL3 is produced by aged neutrophils across cancers and promotes tumor growth
Bolli E, Wirapati P, Hicham M, Xie Y, Siwicki M, Duval F, Goubet A, Kiss M, Zitti B, Zwahlen T, Mcdowell S, Bill R, Angerani S, Engblom C, Anderson S, Jiang A, Hartley O, Sykes D, Jankovic M, Fournier N, Gunzer M, Tarussio D, Tissot S, Sadow P, Faquin W, Sade-Feldman M, Weissleder R, Pai S, Mercier F, Manguso R, Pittet M. CCL3 is produced by aged neutrophils across cancers and promotes tumor growth. Cancer Cell 2026, 44: 624-640.e12. PMID: 41650972, DOI: 10.1016/j.ccell.2026.01.006.Peer-Reviewed Original ResearchConceptsTumor-associated neutrophilsPan-cancer analysisFunctional driversHypoxic tumor nichesPro-tumor neutrophilsMechanistic perturbationsPhenotypic diversityTranscriptional programsLow transcriptionHypoxic tumor regionsAged neutrophilsNeutrophil biologyHypoxic adaptationMurine tumorsTumor nicheGrowing tumorsDifferentiation trajectoriesTumor growthScRNAseq datasetsPan-CancerCancer typesTumorNeutrophilsTumor regionCancer
2025
Positioning and reversible suppression of CCR7+ dendritic cells in perivascular tumor niches shape cancer immunity
Zitti B, Duval F, Wirapati P, Hicham M, Xie Y, Oh J, Hoelzl J, Meiser P, Varrone M, Peterson H, Cianciaruso C, Bill R, Bayerl F, Bolli E, Goubet A, Kiss M, McDowell S, Cheng P, Celestini D, Terzic J, Zwahlen T, Alouche N, Zouggari N, Tarussio D, Tissot S, Nunes-Hasler P, Mino-Kenudson M, Lanuti M, Faquin W, Sadow P, Tille J, Labidi-Galy S, Garris C, Hugues S, Petrova T, Ludewig B, Quezada S, Luther S, Mempel T, Ciriello G, Pai S, Michielin O, Böttcher J, Weissleder R, Pittet M. Positioning and reversible suppression of CCR7+ dendritic cells in perivascular tumor niches shape cancer immunity. Immunity 2025, 59: 161-176.e12. PMID: 41421339, PMCID: PMC12882814, DOI: 10.1016/j.immuni.2025.11.020.Peer-Reviewed Original ResearchConceptsDendritic cellsCD40 expressionCD8+ T cell activationAntitumor T-cell responsesReversible suppressionTreg cell depletionAnti-PD-1Co-inhibitory moleculesT cell responsesAnalysis of human cancersT cell activationIntravital analysisIL-12 productionAntitumor immunityTumor controlCancer immunotherapyCD4+Co-stimulatoryCancer immunityPerivascular clustersTumor nicheIL-12Therapeutic efficacyMouse modelCell depletionThe science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee
Coukos G, Donia M, Gastman B, Goff S, Gros A, Harari A, Hernandez S, Ito F, Maker A, Mullinax J, Murthy P, Pai S, Prabhakaran S, Restifo N, Silver N, Smith P, Turcotte S, Wagner P, Yang J, Lotze M. The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee. Journal For ImmunoTherapy Of Cancer 2025, 13: e013420. PMID: 41320228, DOI: 10.1136/jitc-2025-013420.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesImmune checkpoint blockadeClinical outcomesNon-myeloablativeApplication of immune checkpoint blockadeQuantity of tumor-infiltrating lymphocytesTumor-Infiltrating Lymphocyte TherapyAdoptive T cell therapyTransferred T cellsInterleukin-2 administrationT-cell therapySuppressive tumor microenvironmentCancer-associated inflammationAdaptive immune responsesCheckpoint blockadeHot tumorsCold tumorsHomeostatic proliferationEpithelial neoplasmsCancer immunologySurgery CommitteeTIL-ACTTumor microenvironmentT cellsSolid tumors93 Spatial analysis of head and neck squamous cell cancer tumor microenvironment identifies predictors of pembrolizumab therapy
Oh J, Hoelzl J, Carlson J, Bill R, Peterson H, Faquin W, Pittet M, Pai S, Weissleder R. 93 Spatial analysis of head and neck squamous cell cancer tumor microenvironment identifies predictors of pembrolizumab therapy. 2025, a105-a105. DOI: 10.1136/jitc-2025-sitc2025.0093.Peer-Reviewed Original ResearchIn Response to A Clinical Consensus Statement on Pulmonary Recurrent Respiratory Papillomatosis
Kohli N, Pai S, Buckingham J, Carter Y, Saba N, Hung Y, Berkowitz D, Best S, Davis K, Morton C, Popler J, Pransky S, Piccione J, Smith D, Venkatramani R, Stiff M, Buchinsky F, Sidell D. In Response to A Clinical Consensus Statement on Pulmonary Recurrent Respiratory Papillomatosis. The Laryngoscope 2025, 136: e53-e54. PMID: 41174897, DOI: 10.1002/lary.70233.Peer-Reviewed Original ResearchAmerican College of Radiology–Developed Thyroid Imaging Reporting and Data System 3, 4, and 5 thyroid nodules are distinctive by cytology, genetic imprints, and histology
Yu S, Wang M, Langdon J, Zhao J, Pai S, Sinard J, Cai G, Prasad M, Adeniran A. American College of Radiology–Developed Thyroid Imaging Reporting and Data System 3, 4, and 5 thyroid nodules are distinctive by cytology, genetic imprints, and histology. Cancer Cytopathology 2025, 133: e70050. PMID: 41021263, DOI: 10.1002/cncy.70050.Peer-Reviewed Original ResearchConceptsTI-RADS 3Papillary thyroid carcinomaTI-RADS 5TI-RADS 4Risk of malignancyThyroid Imaging ReportingTI-RADSResected nodulesThyroid nodulesImaging ReportingLow risk of malignancyAmerican CollegeLow riskAssociated with high mortalitySuspicious thyroid nodulesHigh-risk mutationsFine-needle aspirationLow malignancy riskHigh-resolution ultrasoundMalignancy rateMalignancy riskThyroid carcinomaHistological featuresClinical dataMolecular testingA Clinical Consensus Statement on Pulmonary Recurrent Respiratory Papillomatosis
Kohli N, Pai S, Buckingham J, Carter Y, Saba N, Hung Y, Berkowitz D, Best S, Davis K, Morton C, Popler J, Pransky S, Piccione J, Smith D, Venkatramani R, Stiff M, Buchinsky F, Sidell D. A Clinical Consensus Statement on Pulmonary Recurrent Respiratory Papillomatosis. The Laryngoscope 2025, 135: 4642-4650. PMID: 40747774, DOI: 10.1002/lary.32463.Peer-Reviewed Original ResearchRecurrent respiratory papillomatosisRespiratory papillomatosisRisk of malignant transformationMultidisciplinary expert consensusClinical consensus statementHPV typesSystemic therapySystemic treatmentThoracic surgeonsPediatric otolaryngologistsPulmonary lesionsMalignant transformationDisease progressionConsensus statementTreatment of orphan diseasesOrphan diseaseConsensus groupDiagnosisLevel V.Expert consensusPapillomatosisTreatmentMultidisciplinary teamDiseaseLiterature reviewCan the co-localization of CD8+, PD-1, PD-L1 AND PD-L2 patterns provide guidance in clinical evolution of patients with head and neck cutaneous squamous cell carcinoma?
Bento G, de Oliveira Santos A, Matos L, Faquin W, Pai S, Cernea C. Can the co-localization of CD8+, PD-1, PD-L1 AND PD-L2 patterns provide guidance in clinical evolution of patients with head and neck cutaneous squamous cell carcinoma? Brazilian Journal Of Otorhinolaryngology 2025, 91: 101632. PMID: 40413814, PMCID: PMC12151684, DOI: 10.1016/j.bjorl.2025.101632.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellCD8-Positive T-LymphocytesCross-Sectional StudiesFemaleHead and Neck NeoplasmsHumansMaleMiddle AgedProgrammed Cell Death 1 Ligand 2 ProteinProgrammed Cell Death 1 ReceptorRetrospective StudiesSkin NeoplasmsSquamous Cell Carcinoma of Head and NeckConceptsHead and neck cutaneous squamous cell carcinomaCutaneous squamous cell carcinomaNeck cutaneous squamous cell carcinomaCD8+ infiltrationPD-1/PD-L1Immune checkpoint axisSquamous cell carcinomaPD-1PD-L1PD-L2Checkpoint axisCell carcinomaClinical evolutionHigh-risk cutaneous squamous cell carcinomaManagement of cutaneous squamous cell carcinomaClinical managementHost anti-tumor immune responseHazard ratioPD-1/PD-L1/PD-L2Anti-tumor immune responseClinical evolution of patientsPD-L1/PD-L2Cox regression methodEvolution of patientsCo-localizationSpatial analysis identifies DC niches as predictors of pembrolizumab therapy in head and neck squamous cell cancer
Oh J, Hoelzl J, Carlson J, Bill R, Peterson H, Faquin W, Pittet M, Pai S, Weissleder R. Spatial analysis identifies DC niches as predictors of pembrolizumab therapy in head and neck squamous cell cancer. Cell Reports Medicine 2025, 6: 102100. PMID: 40311615, PMCID: PMC12147904, DOI: 10.1016/j.xcrm.2025.102100.Peer-Reviewed Original ResearchConceptsHead and neck squamous cell carcinomaCombined positive scoreImmune cell expressionTumor microenvironmentPembrolizumab therapyPD-L1Dendritic cellsResponse to anti-programmed cell death protein 1Anti-programmed cell death protein 1Expression of programmed death-ligand 1Head and neck squamous cell cancerHead and neck squamous cell carcinoma tumorsCell death protein 1Neck squamous cell carcinomaDeath-ligand 1Local tumor microenvironmentSquamous cell cancerSquamous cell carcinomaCell cancerCell carcinomaPatient survivalTreatment efficacyProtein 1Tissue sectionsTumor
Academic Achievements & Community Involvement
Clinical Care
Overview
Sara Isabel Pai, MD, PhD, is a surgical oncologist who specializes in head and neck cancers associated with human papillomavirus (HPV), and in thyroid and parathyroid cancers/disorders. She uses a combination of surgical techniques and immunotherapy to improve patient outcomes.
“My personal goal for my career in medicine is to make a meaningful difference in people's lives. I strive to achieve this daily through patient care, as well as by impacting patients I may not meet personally through my research and the training of the next generation of surgeon-scientists.”
As a professor at Yale School of Medicine, Dr. Pai’s research focuses on cancer immunotherapy. She is particularly interested in understanding how HPV evades the immune system and aims to develop strategies to reactivate the immune response against HPV-related cancer cells. Her work has led to the Food and Drug Administration’s orphan drug designation for pembrolizumab in treating recurrent respiratory papillomatosis (RRP), a rare condition caused by HPV.
Dr. Pai has led several investigator-initiated and industry clinical trials and has over 120 publications in peer-reviewed journals. She serves as Senior Editor for Cancer Research. Dr. Pai completed her medical and doctoral degrees at Johns Hopkins University School of Medicine, focusing on cancer immunology and vaccines. She completed her residency in otolaryngology-head and neck surgery at Johns Hopkins Hospital.
Clinical Specialties
Fact Sheets
Head and Neck Cancer
Learn More on Yale Medicine
Board Certifications
Otolaryngology - Head & Neck Surgery
- Certification Organization
- AB of Otolaryngology - Head and Neck Surgery
- Latest Certification Date
- 2018
- Original Certification Date
- 2008
News
News
- January 07, 2025
Yale Surgeon-Scientist Secures FDA Orphan Drug Designation for Pembrolizumab in Rare Respiratory Disease
- October 17, 2024
Head and Neck Surgery at Smilow Cancer Hospital
- April 16, 2024
Yale-NY Regional Head & Neck Translational Research Symposium
- November 28, 2023
Department of Surgery Welcomes 16 Faculty & 9 Staff
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Otolaryngology Surgery
330 Cedar Street, PO Box 208041
New Haven, CT 06520-8041
United States
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