Immune Checkpoint Blockade Induces Gut Microbiota Translocation That Augments Extraintestinal Anti-Tumor Immunity

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dc.contributor.advisorYan, Nanen
dc.contributor.committeeMemberKoh, Andrew Y.en
dc.contributor.committeeMemberHooper, Lora V.en
dc.contributor.committeeMemberWinter, Sebastian E.en
dc.creatorChoi, Yongbinen
dc.creator.orcid0000-0002-0329-3895
dc.date.accessioned2023-06-07T18:16:41Z
dc.date.available2023-06-07T18:16:41Z
dc.date.created2023-05
dc.date.issued2023-05-01T05:00:00.000Z
dc.date.submittedMay 2023
dc.date.updated2023-06-07T18:16:42Z
dc.description.abstractGut microbiota are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anti-cancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut microbiota into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues which promote optimal anti-tumor T-cell responses in both the tumor-draining lymph nodes (TDLN) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into MLN and TDLN, diminished DC and effector CD8+ T cell responses, and attenuated response to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anti-cancer immunity.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1381370294
dc.identifier.urihttps://hdl.handle.net/2152.5/10070
dc.language.isoenen
dc.subjectMelanomaen
dc.subjectGastrointestinal Microbiomeen
dc.titleImmune Checkpoint Blockade Induces Gut Microbiota Translocation That Augments Extraintestinal Anti-Tumor Immunityen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineImmunologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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