title: T cell Bim levels reflect responses to anti-PD-1 cancer therapy.
abstract: Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti-PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti-PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti-PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti-PD-1 therapy, although future prospective analyses are needed to validate its utility.
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Roxana S
authors.initials: RS
authors.lastname: Dronca
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Harrington
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Siyu
authors.initials: S
authors.lastname: Cao
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kottschade
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: McWilliams
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Block
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Nevala
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Thompson
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Mansfield
authors.affiliation: Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Sean S
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA; Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong