Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma.

Autor:	Shu DH; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Ho WJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Kagohara LT; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Girgis A; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Shin SM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Danilova L; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Lee JW; Department of Pathology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Sidiropoulos DN; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Mitchell S; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Munjal K; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Howe K; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Bendinelli KJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Kartalia E; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Qi H; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Mo G; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Montagne J; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Leatherman JM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Lopez-Vidal TY; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Zhu Q; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Huff AL; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Yuan X; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Hernandez A; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Coyne EM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Zaidi N; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Zabransky DJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Engle LL; Department of Dermatology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; The Mark Foundation Center for Advanced Genomics and Imaging, Johns Hopkins University, Baltimore, MD, USA.; Bloomberg∼Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Ogurtsova A; Department of Dermatology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; The Mark Foundation Center for Advanced Genomics and Imaging, Johns Hopkins University, Baltimore, MD, USA.; Bloomberg∼Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Baretti M; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Laheru D; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA., Durham JN; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Wang H; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Sunshine JC; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Department of Dermatology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; The Mark Foundation Center for Advanced Genomics and Imaging, Johns Hopkins University, Baltimore, MD, USA.; Bloomberg∼Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Johnston RJ; Genentech Inc, South San Francisco, CA, USA., Deutsch JS; Department of Dermatology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; The Mark Foundation Center for Advanced Genomics and Imaging, Johns Hopkins University, Baltimore, MD, USA.; Bloomberg∼Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Taube JM; Department of Dermatology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; The Mark Foundation Center for Advanced Genomics and Imaging, Johns Hopkins University, Baltimore, MD, USA.; Bloomberg∼Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Anders RA; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.; Department of Pathology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA., Jaffee EM; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA.; Bloomberg∼Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Fertig EJ; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA. ejfertig@jhmi.edu.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA. ejfertig@jhmi.edu.; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA. ejfertig@jhmi.edu.; Department of Applied Mathematics and Statistics, Johns Hopkins University Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA. ejfertig@jhmi.edu., Yarchoan M; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA. mark.yarchoan@jhmi.edu.; Convergence Institute, Johns Hopkins University, Baltimore, MD, USA. mark.yarchoan@jhmi.edu.; Bloomberg∼Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. mark.yarchoan@jhmi.edu.
Jazyk:	angličtina
Zdroj:	Nature immunology [Nat Immunol] 2024 Nov; Vol. 25 (11), pp. 2110-2123. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1038/s41590-024-01992-w
Abstrakt:	Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers. Collectively, these data suggest that TLS can serve as both a prognostic and predictive marker of response to immunotherapy in hepatocellular carcinoma and that late-stage TLS may support T cell memory formation after elimination of a viable tumor. (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze:	MEDLINE
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