Milotay G., Little M., Watson RA., Muldoon D., MacKay S., Kurioka A., Tong O., Taylor CA., Nassiri I., Webb LM., Akin-Adigun O., Bremke J., Ye W., Sun B., Sharma PK., Cooper R., Danielli S., Santo FM., Verge de Los Aires A., Niu G., Cohen L., Ng E., Gilchrist JJ., Chong AY., Mentzer A., Woodcock V., Coupe N., Payne MJ., Youdell M., Middleton MR., Klenerman P., Fairfax BP.

Cytomegalovirus (CMV) is a globally endemic latent herpes virus that profoundly impacts T cell immunity. We investigated the oncological consequences of CMV infection across 341 prospectively recruited patients receiving immune checkpoint blockade (ICB) for melanoma. CMV+ patients with metastatic melanoma (MM) have higher lymphocyte counts, reduced neutrophil to lymphocyte ratio and divergent CD8+ T cell gene expression. Combination anti-CTLA-4/anti-PD-1 ICB, but not single-agent anti-PD-1 ICB, induces cytotoxicity and CMV-associated gene expression in CD8+ T cells from CMV- patients. Correspondingly, overall survival was independent of CMV serostatus in combination anti-CTLA-4/anti-PD-1 ICB recipients (CMV+ hazard ratio for death: 1.02, P = 0.92), whereas CMV+ single-agent anti-PD-1 ICB recipients had improved overall survival (CMV+ hazard ratio for death: 0.37, P

CMV serostatus is associated with improved survival and delayed toxicity onset following anti-PD-1 checkpoint blockade.

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