Increased Tim-3+ T cells in PBMCs during nivolumab therapy correlate with responses and prognosis of advanced esophageal squamous cell carcinoma patients

Ryo Kato, Makoto Yamasaki, Shinya Urakawa, Kentaro Nishida, Tomoki Makino, Akiko Morimoto-Okazawa, Atsunari Kawashima, Kota Iwahori, Susumu Suzuki, Ryuzo Ueda, Masaki Mori, Taroh Satoh, Yuichiro Doki, Hisashi Wada

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The recent development of immune checkpoint inhibitors for many types of cancers has prompted us to identify markers that predict patients with clinical benefits. Several trials on nivolumab for the treatment of esophageal squamous cell carcinoma (ESCC) have been performed worldwide, and the identification of markers specific to ESCC is urgently needed. We conducted a clinical trial on nivolumab for advanced ESCC (JapicCTI-No.142422) and investigated markers using peripheral blood collected from 20 patients enrolled in our institute, including 1 with a complete response (CR), 5 with a partial response (PR), 6 with a stable disease (SD), and 8 with a progressive disease (PD) as clinical responses. The expression of surface molecules and cytokine production by T cells were analyzed using flow cytometry, and clinicopathological factors and general blood parameters were examined. Albumin, neutrophils, %Tim3, %OX40, %CD103, %CD45RACD27, and IL-1b after the first cycle of nivolumab treatment, but not at baseline, distinguished CR/PR from SD/PD patients. When markers to distinguish longer survivors with nivolumab therapy were analyzed, changes in these levels between baseline and after the first cycle of nivolumab treatment, but not levels at each period, were indicative, similar to the tumor burden. Among them, elevations in %Tim-3+CD4 had a marked impact on survival rates. In conclusion, dynamic elevations in %Tim-3 in T cells in the early period of nivolumab therapy have potential as a marker for the clinical responses and prognosis of advanced ESCC patients.

Original languageEnglish
Pages (from-to)1673-1683
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume67
Issue number11
DOIs
Publication statusPublished - Nov 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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    Kato, R., Yamasaki, M., Urakawa, S., Nishida, K., Makino, T., Morimoto-Okazawa, A., Kawashima, A., Iwahori, K., Suzuki, S., Ueda, R., Mori, M., Satoh, T., Doki, Y., & Wada, H. (2018). Increased Tim-3+ T cells in PBMCs during nivolumab therapy correlate with responses and prognosis of advanced esophageal squamous cell carcinoma patients. Cancer Immunology, Immunotherapy, 67(11), 1673-1683. https://doi.org/10.1007/s00262-018-2225-x