Ctim-08. local immunotherapy with autologous cik cells for high grade gliomas: a pilot study with 20 years follow-up and favorable factors for long-term survival

Abstract BACKGROUND Between November 2002 and March 2004, a pilot study was conducted to evaluate the tolerance and survival following local administration of autologous cytokine-induced killer (CIK) cells through Ommaya reservoirs implanted into the tumor resection cavity in 6 patients with high grade glioma (HGG) at Sun Yat-sen University Cancer Center. METHODS We reviewed the clinicopathological characteristics of these patients and updated their long-term follow-up. Profiles of tumor genome, transcriptome and immune microenvironment were also investigated by genomic target sequencing, RNA sequencing, electrochemiluminescence assay and immunohistochemistry (IHC) staining. RESULTS Four patients died from tumor progression and their overall survival ranged from 10.0 to 33.9 months. Remarkably, 2 patients, including one diagnosed as astrocytoma (IDH1 mutation, WHO 3) and the other diagnosed as diffuse hemispheric glioma H3 G34-mutant (G34-DHG), survived more than 19 years without evidence of recurrence. The distinctive clinical feature of the 2 long-term survivors was tumor gross total resection (GTR) before CIK therapy. Comparing with the short-term survivors, NTRK1 mutation was uniquely present and 353 genes were differentially expressed in the long-term survivors. These differential expression genes were highly associated with immune function. Electrochemiluminescence assay and IHC staining revealed higher expressions of cytokines and lower infiltrations of tumor-associated macrophages in the tumors of the long-term survivors. CONCLUSION These findings suggest that certain HGG patients can acquire long-term survival after local immunotherapy with CIK cells. Tumor GTR before CIK therapy and relatively weaker immunosuppressive tumor microenvironment may be the favorable factors for long-term survival.