Understanding Suboptimal Response to Immune Checkpoint Inhibitors

Mojun Zhu, Henan Zhang, Katrina S. Pedersen, Nathan R. Foster, Brandy L. Jaszewski, Xin Liu, Jacob B. Hirdler, Zesheng An, Tanios S. Bekaii-Saab, Thorvardur R. Halfdanarson, Patrick M. Boland, Yiyi Yan, Joleen H. Hubbard, Wen Wee Ma, Harry H. Yoon, Alexander Revzin, Martin E. Fernandez-Zapico, Michael J. Overman, Robert R. McWilliams, Haidong Dong

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Immune checkpoint inhibitors (ICIs), as a novel class of anticancer therapy, can be more efficacious and less toxic than chemotherapy, but their clinical success is confined to certain tumor types. Elucidating their targets, mechanisms and scope of action, and potential synergism with chemotherapy and/or targeted therapies are critical to widen their clinical indications. Treatment response to an ICI targeting programmed death-1 (anti-PD-1) is sought to be understood here by conducting a preplanned correlative analysis of a phase II clinical trial in patients with small bowel adenocarcinoma (SBA). The cytolytic capacity of circulating immune cells in cancer patients using a novel ex vivo cytotoxicity assay is evaluated, and the utility of circulating biomarkers is investigated to predict and monitor the treatment effect of anti-PD-1. Baseline expression of Bim and NKG7 and upregulation of CX3CR1 in circulating T cells are associated with the clinical benefit of anti-PD-1 in patients with SBA. Overall, these findings suggest that the frequency and cytolytic capacity of circulating, effector immune cells may differentiate clinical response to ICIs, providing a strong rationale to support immune monitoring using patient peripheral blood.

Original languageEnglish
Article number2101319
JournalAdvanced Biology
Issue number4
StatePublished - Apr 2023


  • PD-1
  • circulating biomarker
  • small bowel


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