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Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis.
- Source :
-
Nature communications [Nat Commun] 2021 Mar 04; Vol. 12 (1), pp. 1439. Date of Electronic Publication: 2021 Mar 04. - Publication Year :
- 2021
-
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 <superscript>+</superscript> T cells (T <subscript>EM</subscript> cells). Pre-therapy CD4 <superscript>+</superscript> T <subscript>EM</subscript> 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 <superscript>+</superscript> T <subscript>EM</subscript> expansion. Pre-therapy CD4 <superscript>+</superscript> T <subscript>EM</subscript> expansion predicts hepatitis in CMV-seropositive patients, opening possibilities for avoidance or prevention. 3 of 4 patients with pre-treatment CD4 <superscript>+</superscript> T <subscript>EM</subscript> expansion who received αPD-1 monotherapy instead of αPD-1/αCTLA-4 therapy remained hepatitis-free. 4 of 4 patients with baseline CD4 <superscript>+</superscript> T <subscript>EM</subscript> 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.
- Subjects :
- Antiviral Agents therapeutic use
CD4-Positive T-Lymphocytes transplantation
CD8-Positive T-Lymphocytes immunology
Cytomegalovirus drug effects
Cytomegalovirus immunology
Hepatitis A immunology
Hepatitis A virology
Humans
Immunologic Memory immunology
Melanoma drug therapy
Valganciclovir therapeutic use
Viral Load
CD4-Positive T-Lymphocytes immunology
CTLA-4 Antigen antagonists & inhibitors
Cytomegalovirus Infections drug therapy
Hepatitis A prevention & control
Immune Checkpoint Inhibitors therapeutic use
Programmed Cell Death 1 Receptor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 33664251
- Full Text :
- https://doi.org/10.1038/s41467-021-21572-y