Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer.
Proc Natl Acad Sci U S A
; 117(22): 12288-12294, 2020 06 02.
Article
em En
| MEDLINE
| ID: mdl-32430334
ABSTRACT
PD-1 and PD-L1 act to restrict T cell responses in cancer and contribute to self-tolerance. Consistent with this role, PD-1 checkpoint inhibitors have been associated with immune-related adverse events (irAEs), immune toxicities thought to be autoimmune in origin. Analyses of dermatological irAEs have identified an association with improved overall survival (OS) following anti-PD-(L)1 therapy, but the factors that contribute to this relationship are poorly understood. We collected germline whole-genome sequencing data from IMvigor211, a recent phase 3 randomized controlled trial comparing atezolizumab (anti-PD-L1) monotherapy to chemotherapy in bladder cancer. We found that high vitiligo, high psoriasis, and low atopic dermatitis polygenic risk scores (PRSs) were associated with longer OS under anti-PD-L1 monotherapy as compared to chemotherapy, reflecting the Th17 polarization of these diseases. PRSs were not correlated with tumor mutation burden, PD-L1 immunohistochemistry, nor T-effector gene signatures. Shared genetic factors impact risk for dermatological autoimmunity and anti-PD-L1 monotherapy in bladder cancer.
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MEDLINE
Assunto principal:
Pele
/
Neoplasias da Bexiga Urinária
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article