Circulating effector memory CD8 T-cells predict tumor shrinkage and reflect wasting conditions and immunity in tocilizumab plus gemcitabine/nab-paclitaxel for mPDAC
By: Mitsunaga, Shuichi, Ikeda, Masafumi, Imaoka, Hiroshi, Sasaki, Mitsuhito, Watanabe, Kazuo, Sato, Akihiro, Aoki, Kazunori, Koyama, Shohei, Kayukawa, Yoko, Fujii, Etsuko, Fujitomo, Takashi, Mizuno, Hideaki, Yamaguchi, Kyoko, Sawada, Noriaki, Natori, Osamu, Tsunoda, Hiroyuki, Terao, Kimio

BioMed Central
2026-08-10; doi: 10.1186/s12885-026-16685-w

Abstract

Background

Circulating levels of effector memory CD8 + T cells are associated with a better prognosis in patients with metastatic pancreatic ductal adenocarcinoma. The purpose of this study was to assess the effects of effector memory CD8 + T cells on tumor size and wasting conditions.

Methods

In this open-label, phase 1 study, circulating T cell subsets were analysed to evaluate the impacts of effector memory CD8 + T cells on tumor shrinkage and systemic deterioration. Patients had confirmed metastatic pancreatic ductal adenocarcinoma and experienced disease progression after partial responses to gemcitabine / nanoparticle albumin-bound paclitaxel.

Results

Thirty-four immune cell markers were identified at baseline, Day 9 and Day 28 from the peripheral blood of 10 patients who were treated with tocilizumab 8 mg/kg on Day 1, followed by nanoparticle albumin-bound paclitaxel 100 mg/m2 and gemcitabine 750 mg/m2, on Days 2, 9 and 16 in 28-day cycles. Circulating effector memory CD8 + T cells levels were higher in responders at baseline, were maintained on Days 9 and 28 and were associated with a reduction in the primary pancreatic tumor size. Wasting conditions were relieved and higher levels of effector memory CD8 + T cells at baseline were negatively correlated with percentage body weight loss (r = − 0.498, P = 0.006), nausea scores (r = − 0.437, P = 0.062) and walking disturbance scores (r = − 0.383, P = 0.105).

Conclusions

Baseline levels of effector memory CD8 + T cells are a potential biomarker to predict the therapeutic efficacy of tocilizumab and to evaluate wasting conditions in metastatic pancreatic ductal adenocarcinoma. Further research into the role of effector memory CD8 + T cells in relation to cachexia is required.

Trial registration

The clinical part of the study was registered with the Japan Pharmaceutical Information Center Clinical Trials Information (JapicCTI-194753, registered in May 2019), and the translational research part was registered with the Japan Registry of Clinical Trials (jRCT1030200192, registered in November 2020).

Graphical Abstract




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