Circulating effector memory CD8 + T-cells predict tumor shrinkage and reflect wasting conditions and immunity in tocilizumab plus gemcitabine/nab-paclitaxel for mPDAC

Abstract

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. 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. 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/m 2 and gemcitabine 750 mg/m 2 , 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). 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. 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).