Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells.

Autor:	Wang J; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China., Gai J; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Zhang T; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Niu N; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Qi H; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Quantitative Sciences Division, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Cancer Convergence Institute at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Thomas DL 2nd; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Li K; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Xia T; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Rodriguez C; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Parkinson R; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Cancer Convergence Institute at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Durham J; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Cancer Convergence Institute at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., McPhaul T; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Narang AK; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Anders RA; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Osipov A; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Cedars Sinai Medical Center, Los Angeles, CA, 90048, USA., Wang H; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Quantitative Sciences Division, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Cancer Convergence Institute at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., He J; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Laheru DA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Cancer Convergence Institute at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Herman JM; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Northwell Health System, New Hyde Park, NY, 11042, USA., Lee V; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Jaffee EM; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Cancer Convergence Institute at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Thompson ED; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Zhu Q; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Cancer Convergence Institute at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA., Zheng L; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Skip Viragh Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; The Cancer Convergence Institute at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2024 Feb 09; Vol. 10 (6), pp. eadk1827. Date of Electronic Publication: 2024 Feb 07.
DOI:	10.1126/sciadv.adk1827
Abstrakt:	Radiotherapy is hypothesized to have an immune-modulating effect on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) to sensitize it to anti-PD-1 antibody (a-PD-1) treatment. We collected paired pre- and posttreatment specimens from a clinical trial evaluating combination treatment with GVAX vaccine, a-PD-1, and stereotactic body radiation (SBRT) following chemotherapy for locally advanced PDACs (LAPC). With resected PDACs following different neoadjuvant therapies as comparisons, effector cells in PDACs were found to skew toward a more exhausted status in LAPCs following chemotherapy. The combination of GVAX/a-PD-1/SBRT drives TME to favor antitumor immune response including increased densities of GZMB + CD8 + T cells, T H 1, and T H 17, which are associated with longer survival, however increases immunosuppressive M2-like tumor-associated macrophages (TAMs). Adding SBRT to GVAX/a-PD-1 shortens the distances from PD-1 + CD8 + T cells to tumor cells and to PD-L1 + myeloid cells, which portends prolonged survival. These findings have guided the design of next radioimmunotherapy studies by targeting M2-like TAM in PDACs.
Databáze:	MEDLINE
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