TY - JOUR
T1 - T cell Bim levels reflect responses to anti–PD-1 cancer therapy
AU - Dronca, Roxana S.
AU - Liu, Xin
AU - Harrington, Susan M.
AU - Chen, Lingling
AU - Cao, Siyu
AU - Kottschade, Lisa A.
AU - McWilliams, Robert R.
AU - Block, Matthew S.
AU - Nevala, Wendy K.
AU - Thompson, Michael A.
AU - Mansfield, Aaron S.
AU - Park, Sean S.
AU - Markovic, Svetomir N.
AU - Dong, Haidong
N1 - Publisher Copyright:
© 2016 American Society for Clinical Investigation. All rights reserved.
PY - 2016/5/5
Y1 - 2016/5/5
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.86014
DO - 10.1172/jci.insight.86014
M3 - Article
AN - SCOPUS:85127271744
SN - 2379-3708
VL - 1
JO - JCI Insight
JF - JCI Insight
IS - 6
M1 - e86014
ER -