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Delayed tumor-draining lymph node irradiation preserves the efficacy of combined radiotherapy and immune checkpoint blockade in models of metastatic disease.
Telarovic, Irma; Yong, Carmen S M; Kurz, Lisa; Vetrugno, Irene; Reichl, Sabrina; Fernandez, Alba Sanchez; Cheng, Hung-Wei; Winkler, Rona; Guckenberger, Matthias; Kipar, Anja; Ludewig, Burkhard; Pruschy, Martin.
Afiliación
  • Telarovic I; Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Yong CSM; Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Kurz L; Department of Immunology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Vetrugno I; Institute of Immunobiology, Medical Research Center, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Reichl S; Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Fernandez AS; Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Cheng HW; Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Winkler R; Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Guckenberger M; Institute of Immunobiology, Medical Research Center, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Kipar A; Laboratory for Applied Radiobiology, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Ludewig B; Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Pruschy M; Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Nat Commun ; 15(1): 5500, 2024 Jun 29.
Article en En | MEDLINE | ID: mdl-38951172
ABSTRACT
Cancer resistance to immune checkpoint inhibitors motivated investigations into leveraging the immunostimulatory properties of radiotherapy to overcome immune evasion and to improve treatment response. However, clinical benefits of radiotherapy-immunotherapy combinations have been modest. Routine concomitant tumor-draining lymph node irradiation (DLN IR) might be the culprit. As crucial sites for generating anti-tumor immunity, DLNs are indispensable for the in situ vaccination effect of radiotherapy. Simultaneously, DLN sparing is often not feasible due to metastatic spread. Using murine models of metastatic disease in female mice, here we demonstrate that delayed (adjuvant), but not neoadjuvant, DLN IR overcomes the detrimental effect of concomitant DLN IR on the efficacy of radio-immunotherapy. Moreover, we identify IR-induced disruption of the CCR7-CCL19/CCL21 homing axis as a key mechanism for the detrimental effect of DLN IR. Our study proposes delayed DLN IR as a strategy to maximize the efficacy of radio-immunotherapy across different tumor types and disease stages.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Puntos de Control Inmunológico / Ganglios Linfáticos Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Puntos de Control Inmunológico / Ganglios Linfáticos Límite: Animals / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido