Therapy of solid cancers using T cells and running shoes

Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningfagfællebedømt

Cells of the immune system, e.g., CD8 T cells and Natural killer (NK) cells are capable of recognizing and killing cancer cells. Moreover, several lines of evidence suggest that the naturally elicited anti-cancer immune responses lead to infiltration of immune cells into tumors and the presence of these cells have an impact on disease progression, i.e., overall survival of the patient. Harnessing of the immune system to combat cancer i.e., cancer immunotherapy, is revolutionizing treatment of patients today. To this end, administration of immune check inhibitory monoclonal antibodies is approved for the treatment of several solid cancer indications, and although predictive markers are still missing, patients with a brisk tumor infiltration of immune cells are more prone to respond to treatment. Moreover, immune cells infiltrating into the tumor can be directly utilized in therapy by administration of in vitro expanded tumor infiltrating lymphocytes (TIL). In our clinical trials based on TIL therapy we have experienced massive tumor regressions in melanoma patients, some of which experience potentially curative complete responses. The success of TIL therapy in melanoma, clearly builds on the presence of tumor specific T cells at the tumor site, and underscores the need to define ways as how to increase immune cell infiltration to the tumor site. Regular exercise reduces the risk of cancer and disease recurrence, by largely unknown mechanisms. We recently demonstrated that voluntary wheel running showed over 60% reduction in tumor incidence and growth across several murine tumor models. Microarray analysis revealed exercise-induced up-regulation of pathways associated with immune function, prompting further investigations. Immune cell infiltration was significantly increased in tumors from exercising mice, and depletion of NK cells enhanced tumor growth and blunted the exercise-dependent suppression. Moreover, NK cells were engaged through an epinephrine-dependent mobilization, and blockade of this pathway by β-adrenergic blockade blunted the exercise-dependent tumor inhibition. Together these results link exercise with improved immunological control of tumor progression, suggesting that exercise could be a beneficial partner for immunotherapy.
OriginalsprogEngelsk
ArtikelnummerK6
TidsskriftJournal of Translational Medicine
Vol/bind15
Udgave nummerS1
Antal sider1
ISSN1479-5876
DOI
StatusUdgivet - 2017
BegivenhedImmunotherary Bridge 2016 - Royal Continental Hotel, Naples, Italien
Varighed: 30 nov. 20163 dec. 2016
Konferencens nummer: 2

Konference

KonferenceImmunotherary Bridge 2016
Nummer2
LokationRoyal Continental Hotel
LandItalien
ByNaples
Periode30/11/201603/12/2016

ID: 184172596