Hutchinson, James A. and Kronenberg, Katharina and Riquelme, Paloma and Wenzel, Juergen J. and Glehr, Gunther and Schilling, Hannah-Lou and Zeman, Florian and Evert, Katja and Schmiedel, Martin and Mickler, Marion and Drexler, Konstantin and Bitterer, Florian and Cordero, Laura and Beyer, Lukas and Bach, Christian and Koestler, Josef and Burkhardt, Ralph and Schlitt, Hans J. and Hellwig, Dirk and Werner, Jens M. and Spang, Rainer and Schmidt, Barbara and Geissler, Edward K. and Haferkamp, Sebastian (2021) Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis. NATURE COMMUNICATIONS, 12 (1): 1439. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)Abstract
Treatment of advanced melanoma with combined PD-1/CTLA-4 blockade commonly causes serious immune-mediated complications. Here, we identify a subset of patients predisposed to immune checkpoint blockade-related hepatitis who are distinguished by chronic expansion of effector memory CD4(+) T cells (T-EM cells). Pre-therapy CD4(+) T-EM cell expansion occurs primarily during autumn or winter in patients with metastatic disease and high cytomegalovirus (CMV)-specific serum antibody titres. These clinical features implicate metastasis-dependent, compartmentalised CMV reactivation as the cause of CD4(+) T-EM expansion. Pre-therapy CD4(+) T-EM expansion predicts hepatitis in CMV-seropositive patients, opening possibilities for avoidance or prevention. 3 of 4 patients with pre-treatment CD4(+) T-EM expansion who received alpha PD-1 monotherapy instead of alpha PD-1/alpha CTLA-4 therapy remained hepatitis-free. 4 of 4 patients with baseline CD4(+) T-EM expansion given prophylactic valganciclovir and alpha PD-1/alpha CTLA-4 therapy remained hepatitis-free. Our findings exemplify how pathogen exposure can shape clinical reactions after cancer therapy and how this insight leads to therapeutic innovations. Checkpoint blocking therapies are used to treat metastatic melanoma, but can have adverse immune-mediated effects, including liver pathology. Here the authors identify an expanded pool of CD4(+) effector memory T cells resulting from prior CMV exposure as a risk factor for this adverse effect in these patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IPILIMUMAB; NIVOLUMAB; STIMULATION; EXPANSION; SURVIVAL; MELANOMA; CTLA-4; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für Röntgendiagnostik Medicine > Abteilung für Nuklearmedizin Medicine > Zentren des Universitätsklinikums Regensburg > Zentrum für Klinische Studien Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Jul 2022 06:57 |
| Last Modified: | 05 Jul 2022 06:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45591 |
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