[en] Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving
local tumor control and patient overall survival. The neoRT schedule and the timing
of the surgical treatment (ST) are empirically based and influenced by the clinician’s
experience. The current study examines how the sequencing of neoRT and ST affects
metastatic dissemination. In a breast carcinoma model, tumors were exposed to
different neoRT schedules (2x5Gy or 5x2Gy) followed by surgery at day 4 or 11 post-
RT. The impact on the tumor microenvironment and lung metastases was evaluated
through immunohistochemical and flow cytometry analyses.
After 2x5Gy, early ST (at day 4 post-RT) led to increased size and number of lung
metastases as compared to ST performed at day 11. Inversely, after 5x2Gy neoRT,
early ST protected the mice against lung metastases. This intriguing relationship
between tumor aggressiveness and ST timing could not be explained by differences in
classical parameters studied such as hypoxia, vessel density and matrix remodeling.
The study of tumor-related inflammation and immunity reveals an increased
circulating NK cell percentage following neoRT as compared to non irradiated mice.
Then, radiation treatment and surgery were applied to tumor-bearing NOD/SCID mice.
In the absence of NK cells, neoRT appears to increase lung metastatic dissemination
as compared to non irradiated tumor-bearing mice.
Altogether our data demonstrate that the neoRT schedule and the ST timing
affect metastasis formation in a pre-clinical model and points out the potential role
of NK cells. These findings highlight the importance to cautiously tailor the optimal
window for ST following RT.
Disciplines :
Oncology
Author, co-author :
Leroi, Natacha ; Université de Liège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Sounni, Nor Eddine ; Université de Liège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Van Overmeire, Eva; Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels, Belgium
Blacher, Silvia ; Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Van Ginderachter, Jo; Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussels, Belgium
Lallemand, François ; Université de Liège > Département des sciences cliniques > Radiothérapie
LENAERTS, Eric ; Centre Hospitalier Universitaire de Liège - CHU > Département de Physique Médicale
COUCKE, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > Service médical de radiothérapie
Noël, Agnès ✱; Laboratory of Tumor and Development Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGACancer), University of Liege, Belgium
MARTINIVE, Philippe ✱; Centre Hospitalier Universitaire de Liège - CHU > Service médical de radiothérapie
✱ These authors have contributed equally to this work.
Language :
English
Title :
The timing of surgery after neoadjuvant radiotherapy influences tumor dissemination in a preclinical model
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