TY - JOUR
T1 - Increased Tim-3+ T cells in PBMCs during nivolumab therapy correlate with responses and prognosis of advanced esophageal squamous cell carcinoma patients
AU - Kato, Ryo
AU - Yamasaki, Makoto
AU - Urakawa, Shinya
AU - Nishida, Kentaro
AU - Makino, Tomoki
AU - Morimoto-Okazawa, Akiko
AU - Kawashima, Atsunari
AU - Iwahori, Kota
AU - Suzuki, Susumu
AU - Ueda, Ryuzo
AU - Mori, Masaki
AU - Satoh, Taroh
AU - Doki, Yuichiro
AU - Wada, Hisashi
N1 - Funding Information:
Funding This study was performed as a research program of the Project for the Development of Innovative Research on Cancer Therapeutics (P-Direct), The Japan Agency for Medical Research and Development (AMED), and was also supported by the Practice Research for Innovative Cancer Control (15ck0106159h) from AMED. The ONO-4538-07 clinical trial was funded by Ono Pharmaceuticals and Bristol-Myers Squibb.
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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, %CD45RA−CD27−, 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.
AB - 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, %CD45RA−CD27−, 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.
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U2 - 10.1007/s00262-018-2225-x
DO - 10.1007/s00262-018-2225-x
M3 - Article
C2 - 30128737
AN - SCOPUS:85051807821
VL - 67
SP - 1673
EP - 1683
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 11
ER -