| Autor: |
Michael H. Muders, Joanna Mangana, Ewout Landeloos, Michael Hölzel, Fiamma Berner, Florian Rambow, Lukas Flatz, Thomas Mayr, Dimo Dietrich, Greet Bervoets, Sandra S. Ring, Rebekka Niederer, Wolfram Jochum, Oliver Bechter, David Bomze, Antonio Cozzio, Claus Garbe, Omar Ali, Jean-Christophe Marine, Tobias Bald, Sandra N. Freiberger, Stefan Diem, Mitchell P. Levesque, Jennifer Lansdberg, Reinhard Dummer, Burkhard Ludewig, Marie-Therese Abdou, Maries van den Broek, Oltin T Pop, Joanna Poźniak, Mirjam Fässler, Thomas Tüting |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
T cells are critical in cancer immune surveillance but they can also shape tumor immunogenicity, described as cancer immunoediting. Melanoma patients commonly harbor T cells recognizing melanocyte differentiation antigens (MDAs). However, the roles of MDA-specific T cells in shaping melanoma immunogenicity and the response to immune checkpoint inhibition remain elusive. Here, we prospectively profiled peripheral CD8+ T cells from 27 stage IV patients before initiation of checkpoint inhibitor therapy. Clinical failure was associated with increased MDA-specific CD8+ T cells and reduced tumor MDA expression pretreatment. In nonresponders, decreased tumor MDA expression was concomitant with a dedifferentiated melanoma phenotype. We confirmed in 30 stage III patients that individuals with relapse disease during adjuvant anti-PD-1 therapy demonstrated a significantly higher incidence of dedifferentiated tumors pretreatment than individuals without recurrence. Thus, MDA-directed CD8+ T cells are associated with a dedifferentiated phenotype and reduced clinical response to checkpoint inhibitor therapy suggesting immunoediting as an important resistance mechanism. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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