Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis
| Autor: | Paloma Riquelme, Konstantin Drexler, Hans J. Schlitt, Marion Mickler, Martin Schmiedel, Josef Koestler, Laura Cordero, Jens M. Werner, Sebastian Haferkamp, Jürgen J. Wenzel, Dirk Hellwig, Christian Bach, Katja Evert, Gunther Glehr, Edward K. Geissler, James A. Hutchinson, Florian Zeman, Ralph Burkhardt, Lukas Philipp Beyer, Rainer Spang, Hannah-Lou Schilling, Barbara Schmidt, Katharina Kronenberg, F Bitterer |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Immunotherapy Melanoma Predictive markers Tumour immunology Viral host response Science Programmed Cell Death 1 Receptor Congenital cytomegalovirus infection 610 Medizin Cytomegalovirus General Physics and Astronomy CD8-Positive T-Lymphocytes Predictive markers Antiviral Agents Article General Biochemistry Genetics and Molecular Biology Virus 03 medical and health sciences 0302 clinical medicine medicine Humans Valganciclovir CTLA-4 Antigen ddc:610 Immune Checkpoint Inhibitors Melanoma Hepatitis Multidisciplinary business.industry Viral host response General Chemistry Hepatitis A Viral Load medicine.disease Immune checkpoint Blockade 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cytomegalovirus Infections Immunology Tumour immunology Immunotherapy business Immunologic Memory Memory T cell Viral load medicine.drug |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) |
| Popis: | 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 (TEM cells). Pre-therapy CD4+ TEM 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+ TEM expansion. Pre-therapy CD4+ TEM expansion predicts hepatitis in CMV-seropositive patients, opening possibilities for avoidance or prevention. 3 of 4 patients with pre-treatment CD4+ TEM expansion who received αPD-1 monotherapy instead of αPD-1/αCTLA-4 therapy remained hepatitis-free. 4 of 4 patients with baseline CD4+ TEM expansion given prophylactic valganciclovir and αPD-1/αCTLA-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. |
| Databáze: | OpenAIRE |
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