Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis

Hutchinson JA, Kronenberg K, Riquelme P, Wenzel JJ, Glehr G, Schilling HL, Zeman F, Evert K, Schmiedel M, Mickler M, Drexler K, Bitterer F, Cordero L, Beyer L, Bach C, Koestler J, Burkhardt R, Schlitt HJ, Hellwig D, Werner JM, Spang R, Schmidt B, Geissler EK, Haferkamp S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 12

Article Number: 1439

Journal Issue: 1

DOI: 10.1038/s41467-021-21572-y

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 (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.

Authors with CRIS profile

Christian Bach Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE) Universität Regensburg DE Germany (DE)

How to cite

APA:

Hutchinson, J.A., Kronenberg, K., Riquelme, P., Wenzel, J.J., Glehr, G., Schilling, H.L.,... Haferkamp, S. (2021). Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-21572-y

MLA:

Hutchinson, James A., et al. "Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis." Nature Communications 12.1 (2021).

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