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Tissue-specific Tregs in cancer metastasis:opportunities for precision immunotherapy

Cellular & Molecular Immunology 2022年第1期19卷 33-45页

作者： Laura A.Huppert Michael D.Green Luke Kim Christine Chow yan leyfman Adil I.Daud James C.Lee Division of Hematology/Oncology Department of MedicineUniversity of CaliforniaSan FranciscoSan FranciscoCAUSA Department of Radiation Oncology University of Michigan School of MedicineAnn ArborMIUSA Veterans Affairs Ann Arbor Healthcare System Ann ArborMIUSA University of California San Francisco School of MedicineSan FranciscoCAUSA Penn State College of Medicine HersheyPAUSA Parker Institute for Cancer Immunotherapy San FranciscoCAUSA

Decades of advancements in immuno-oncology have enabled the development of current immunotherapies,which provide longterm treatment responses in certain metastatic cancer ***,cures remain infrequent,and most patients ultimately succumb to treatment-refractory metastatic *** insights suggest that tumors at certain organ sites exhibit distinctive response patterns to immunotherapy and can even reduce antitumor immunity within anatomically distant tumors,suggesting the activation of tissue-specific immune tolerogenic mechanisms in some cases of therapy *** immune cells known as regulatory T cells(Tregs)are present within all tissues in the body and coordinate the suppression of excessive immune activation to curb autoimmunity and maintain immune *** the high volume of research on Tregs,the findings have failed to reconcile tissue-specific Treg functions in organs,such as tolerance,tissue repair,and regeneration,with their suppression of local and systemic tumor immunity in the context of immunotherapy *** improve the understanding of how the tissue-specific functions of Tregs impact cancer immunotherapy,we review the specialized role of Tregs in clinically common and challenging organ sites of cancer metastasis,highlight research that describes Treg impacts on tissue-specific and systemic immune regulation in the context of immunotherapy,and summarize ongoing work reporting clinically feasible strategies that combine the specific targeting of Tregs with systemic cancer *** knowledge of Tregs in the framework of their tissue-specific biology and clinical sites of organ metastasis will enable more precise targeting of immunotherapy and have profound implications for treating patients with metastatic cancer.

关键词： Tissue Tregs Immunotherapy Organ-specific tolerance Metastasis Cancer

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