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Modeling T cell temporal response to cancer immunotherapy rationalizes development of combinatorial treatment protocols.
Barboy, Oren; Bercovich, Akhiad; Li, Hanjie; Eyal-Lubling, Yaniv; Yalin, Adam; Shapir Itai, Yuval; Abadie, Kathleen; Zada, Mor; David, Eyal; Shlomi-Loubaton, Shir; Katzenelenbogen, Yonatan; Jaitin, Diego Adhemar; Gur, Chamutal; Yofe, Ido; Feferman, Tali; Cohen, Merav; Dahan, Rony; Newell, Evan W; Lifshitz, Aviezer; Tanay, Amos; Amit, Ido.
Afiliación
  • Barboy O; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Bercovich A; Department of Computer Science and Applied Mathematics and Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Li H; Department of Synthetic Immunology, Shenzhen Institutes of Advanced Technology, Shenzhen, China.
  • Eyal-Lubling Y; Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
  • Yalin A; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Shapir Itai Y; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Abadie K; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Zada M; Department of Bioengineering, University of Washington, Seattle, WA, USA.
  • David E; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Shlomi-Loubaton S; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Katzenelenbogen Y; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Jaitin DA; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Gur C; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Yofe I; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Feferman T; The Hebrew University, Jerusalem, Israel.
  • Cohen M; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Dahan R; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Newell EW; Department of Clinical Microbiology and Immunology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Lifshitz A; Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • Tanay A; Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
  • Amit I; Department of Computer Science and Applied Mathematics and Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Nat Cancer ; 5(5): 742-759, 2024 May.
Article en En | MEDLINE | ID: mdl-38429414
ABSTRACT
Successful immunotherapy relies on triggering complex responses involving T cell dynamics in tumors and the periphery. Characterizing these responses remains challenging using static human single-cell atlases or mouse models. To address this, we developed a framework for in vivo tracking of tumor-specific CD8+ T cells over time and at single-cell resolution. Our tools facilitate the modeling of gene program dynamics in the tumor microenvironment (TME) and the tumor-draining lymph node (tdLN). Using this approach, we characterize two modes of anti-programmed cell death protein 1 (PD-1) activity, decoupling induced differentiation of tumor-specific activated precursor cells from conventional type 1 dendritic cell (cDC1)-dependent proliferation and recruitment to the TME. We demonstrate that combining anti-PD-1 therapy with anti-4-1BB agonist enhances the recruitment and proliferation of activated precursors, resulting in tumor control. These data suggest that effective response to anti-PD-1 therapy is dependent on sufficient influx of activated precursor CD8+ cells to the TME and highlight the importance of understanding system-level dynamics in optimizing immunotherapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Microambiente Tumoral / Inmunoterapia Límite: Animals / Humans Idioma: En Revista: Nat Cancer Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Microambiente Tumoral / Inmunoterapia Límite: Animals / Humans Idioma: En Revista: Nat Cancer Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Reino Unido