TY - JOUR
T1 - JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma
AU - Zak, Jaroslav
AU - Pratumchai, Isaraphorn
AU - Marro, Brett S.
AU - Marquardt, Kristi L.
AU - Zavareh, Reza Beheshti
AU - Lairson, Luke L.
AU - Oldstone, Michael B.A.
AU - Varner, Judith A.
AU - Hegerova, Livia
AU - Cao, Qing
AU - Farooq, Umar
AU - Kenkre, Vaishalee P.
AU - Bachanova, Veronika
AU - Teijaro, John R.
N1 - Publisher Copyright:
Copyright © 2024 the authors, some rights reserved
PY - 2024/6/21
Y1 - 2024/6/21
N2 - Unleashing antitumor T cell activity by checkpoint inhibitor immunotherapy is effective in cancer patients, but clinical responses are limited. Cytokine signaling through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway correlates with checkpoint immunotherapy resistance. We report a phase I clinical trial of the JAK inhibitor ruxolitinib with anti–PD-1 antibody nivolumab in Hodgkin lymphoma patients relapsed or refractory following checkpoint inhibitor immunotherapy. The combination yielded a best overall response rate of 53% (10/19). Ruxolitinib significantly reduced neutrophil-to-lymphocyte ratios and percentages of myeloid suppressor cells but increased numbers of cytokine-producing T cells. Ruxolitinib rescued the function of exhausted T cells and enhanced the efficacy of immune checkpoint blockade in preclinical solid tumor and lymphoma models. This synergy was characterized by a switch from suppressive to immunostimulatory myeloid cells, which enhanced T cell division.
AB - Unleashing antitumor T cell activity by checkpoint inhibitor immunotherapy is effective in cancer patients, but clinical responses are limited. Cytokine signaling through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway correlates with checkpoint immunotherapy resistance. We report a phase I clinical trial of the JAK inhibitor ruxolitinib with anti–PD-1 antibody nivolumab in Hodgkin lymphoma patients relapsed or refractory following checkpoint inhibitor immunotherapy. The combination yielded a best overall response rate of 53% (10/19). Ruxolitinib significantly reduced neutrophil-to-lymphocyte ratios and percentages of myeloid suppressor cells but increased numbers of cytokine-producing T cells. Ruxolitinib rescued the function of exhausted T cells and enhanced the efficacy of immune checkpoint blockade in preclinical solid tumor and lymphoma models. This synergy was characterized by a switch from suppressive to immunostimulatory myeloid cells, which enhanced T cell division.
UR - https://www.scopus.com/pages/publications/85196904450
UR - https://www.scopus.com/inward/citedby.url?scp=85196904450&partnerID=8YFLogxK
U2 - 10.1126/science.ade8520
DO - 10.1126/science.ade8520
M3 - Article
C2 - 38900864
AN - SCOPUS:85196904450
SN - 0036-8075
VL - 384
JO - Science
JF - Science
IS - 6702
M1 - eade8520
ER -
