CDK4/6 Inhibition Promotes Antitumor Immunity through the Induction of T-cell Memory.

التفاصيل البيبلوغرافية
العنوان:	CDK4/6 Inhibition Promotes Antitumor Immunity through the Induction of T-cell Memory.
المؤلفون:	Lelliott EJ; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Kong IY; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia., Zethoven M; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Ramsbottom KM; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Martelotto LG; Single Cell Innovation Laboratory, The University of Melbourne, Parkville, Victoria, Australia., Meyran D; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Université de Paris, INSERM, U976 HIPI Unit, Institut de Recherche Saint-Louis, Paris, France., Zhu JJ; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Costacurta M; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Kirby L; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Sandow JJ; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia., Lim L; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Dominguez PM; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Todorovski I; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Haynes NM; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia., Beavis PA; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Neeson PJ; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Hawkins ED; The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia., McArthur GA; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Parish IA; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Johnstone RW; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Oliaro J; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.; Department of Immunology, Central Clinical School, Monash University, Melbourne, Victoria, Australia., Sheppard KE; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. conor.kearney@petermac.org karen.sheppard@petermac.org stephin.vervoort@petermac.org.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.; Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, Victoria, Australia., Kearney CJ; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. conor.kearney@petermac.org karen.sheppard@petermac.org stephin.vervoort@petermac.org.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia., Vervoort SJ; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. conor.kearney@petermac.org karen.sheppard@petermac.org stephin.vervoort@petermac.org.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
المصدر:	Cancer discovery [Cancer Discov] 2021 Oct; Vol. 11 (10), pp. 2582-2601. Date of Electronic Publication: 2021 May 14.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101561693 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2159-8290 (Electronic) Linking ISSN: 21598274 NLM ISO Abbreviation: Cancer Discov Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Philadelphia, PA : American Association for Cancer Research
مواضيع طبية MeSH:	Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyridines/*therapeutic use, Animals ; Antineoplastic Agents/pharmacology ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cyclin-Dependent Kinase 4/antagonists & inhibitors ; Cyclin-Dependent Kinase 6/antagonists & inhibitors ; Female ; Humans ; Memory T Cells/drug effects ; Mice ; Piperazines/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Pyridines/pharmacology ; Xenograft Model Antitumor Assays
مستخلص:	Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) are an approved treatment for hormone receptor-positive breast cancer and are currently under evaluation across hundreds of clinical trials for other cancer types. The clinical success of these inhibitors is largely attributed to well-defined tumor-intrinsic cytostatic mechanisms, whereas their emerging role as immunomodulatory agents is less understood. Using integrated epigenomic, transcriptomic, and proteomic analyses, we demonstrated a novel action of CDK4/6 inhibitors in promoting the phenotypic and functional acquisition of immunologic T-cell memory. Short-term priming with a CDK4/6 inhibitor promoted long-term endogenous antitumor T-cell immunity in mice, enhanced the persistence and therapeutic efficacy of chimeric antigen receptor T cells, and induced a retinoblastoma-dependent T-cell phenotype supportive of favorable responses to immune checkpoint blockade in patients with melanoma. Together, these mechanistic insights significantly broaden the prospective utility of CDK4/6 inhibitors as clinical tools to boost antitumor T-cell immunity. SIGNIFICANCE: Immunologic memory is critical for sustained antitumor immunity. Our discovery that CDK4/6 inhibitors drive T-cell memory fate commitment sheds new light on their clinical activity, which is essential for the design of clinical trial protocols incorporating these agents, particularly in combination with immunotherapy, for the treatment of cancer. This article is highlighted in the In This Issue feature, p. 2355 . (©2021 American Association for Cancer Research.)
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المشرفين على المادة:	0 (Antineoplastic Agents) 0 (Piperazines) 0 (Protein Kinase Inhibitors) 0 (Pyridines) EC 2.7.11.22 (Cyclin-Dependent Kinase 4) EC 2.7.11.22 (Cyclin-Dependent Kinase 6) G9ZF61LE7G (palbociclib)
تواريخ الأحداث:	Date Created: 20210515 Date Completed: 20220314 Latest Revision: 20220314
رمز التحديث:	20240628
DOI:	10.1158/2159-8290.CD-20-1554
PMID:	33990344
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	2159-8290
DOI:	10.1158/2159-8290.CD-20-1554