A multicenter, open-label, single-arm phase 2 clinical trial found a marker in the blood that identified which patients with advanced esophageal squamous cell carcinoma were most likely to respond to the immune checkpoint inhibitor nivolumab.In esophageal cancer, markers for response to immune checkpoint inhibitors have not been reported yet.

To identify a marker for response, study investigators assessed the peripheral blood from 20 patients enrolled in the trial who had advanced esophageal squamous cell carcinoma who were treated with nivolumab at Osaka University Hospital in Japan. Of those 20 patients, 1 had complete response, 5 had a partial response, 6 had stable disease, and 8 had progressive disease.

The analysis revealed that after the first cycle of nivolumab was complete, the following markers in the blood could distinguish patients with a complete or partial response from those with stable or progressive disease: albumin, neutrophils, %Tim3, %OX40, %CD103, %CD45RA−CD27−, and IL-1b.

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“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,” the study authors wrote. “Among them, elevations in %Tim-3+CD4 had a marked impact on survival rates.” 

On the basis of these findings, the study authors concluded that “dynamic elevations” in %Tim-3 in T cells early on in nivolumab treatment could serve as a marker of response for patients with advanced esophageal squamous cell carcinoma. 


  1. Kato R, Yamasaki M, Urakawa S, et al. Increased Tim-3+ T cells in PBMCs during nivolumab therapy correlate with responses and prognosis of advanced esophageal squamous cell carcinoma patientsCancer Immunol Immunother. 2018;67(11):1673-1683. doi: 10.1007/s00262-018-2225-x