Publikationsdatenbank

The immune system prevents recurrence of transplanted but not autochthonous antigenic tumors after oncogene inactivation therapy (2017)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Anders, Kathleen (WE 12)

Kershaw, Olivia (WE 12)

Larue, Lionel (WE 12)

Gruber, Achim Dieter (WE 12)

Blankenstein, Thomas (WE 12)

Quelle

International Journal of Cancer

Bandzählung: 141

Heftzählung: 12

Seiten: 2551 – 2561

ISSN: 1097-0215

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.31009

DOI: 10.1002/ijc.31009

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Targeted oncogene inactivation by small molecule inhibitors can be very effective but tumor recurrence is a frequent problem in the clinic. Therapy by inactivation of the cancer‐driving oncogene in transplanted tumors was shown to be augmented in the presence of T cells. However, these experiments did not take into account the long‐term, usually tolerogenic, interaction of de novo malignancies with the immune system. Here, we employed mice, in which SV40 large T (Tag) and firefly luciferase (Luc) as fusion protein (TagLuc) could be regulated with the Tet‐on system and upon activation resulted in tumors after a long latency. TagLuc inactivation induced profound tumor regression, demonstrating sustained oncogene addiction. While tumor relapse after TagLuc inactivation was prevented in immunocompetent mice bearing transplanted tumors, autochthonous tumors relapsed or recurred after therapy discontinuation indicating that the immune system that coevolved with the malignancy over an extended period of time lost the potency to mount an efficient anti‐tumor immune response. By contrast, adoptively transferred CD8+ T cells targeting the cancer‐driving oncogene eradicated recurrent autochthonous tumors, highlighting a suitable therapy option in a clinically relevant model.