Immune-Related Factors in the Clinical Management of High Grade Glioma (HGG) — The Association Specialists
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Immune-Related Factors in the Clinical Management of High Grade Glioma (HGG) (310)

Nicole Parker 1 , Rowan Ikin 1 , Chris Weir 1 , Lyndsay Peters 1 2 , Viive Howell 1 , Helen Wheeler 3
  1. Kolling Institute of Medical Research, St Leonards, NSW, Australia
  2. Haematology, Royal North Shore Hospital, St Leonards, NSW, Australia
  3. Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia

Background: High grade gliomas (HGG) are primary brain tumours with a poor prognosis. On average, only 9% of patients with grade IV glioma survive 5 years beyond diagnosis. We hypothesise that this poor outcome may be due in part to circulating immune suppressor cells and inflammatory factors protecting glioma cells from immune attack. 

Aim: To determine the effect of current standard of care treatment (temozolomide chemotherapy and concurrent radiation therapy) on immune profiles (humoral and cellular) by monitoring levels longitudinally during treatment. To correlate immune profile with indicators of patient outcome and disease progression.

Methods: Following informed consent under an ethically approved protocol,blood was collected at multiple timepoints from HGG patients receiving treatment at RNSH (n=55 cases) and normal healthy volunteers (n=16). Lymphoid cell subsets, T regulatory cells and myeloid cell subsets (including myeloid derived suppressor cells (MDSCs) were analysed by FACS. Levels of inflammatory cytokines in patient and control plasma samples were measured using a Bio-Plex Cytokine 27-plex array. 

Results: Circulating CD4 T cells decreased by a median of 35% between pretreatment and the end of the first cycle of concurrent therapy. CD4 T cell count was also lower in patients with active disease versus non-progressive disease (p<0.001).  Monocytic MDSCs (CD14+/CD33+/HLA-DRneg) were elevated in patients at pretreatment and wk4 RT, but were present at significantly lower levels at cycle 1 of chemotherapy (p<0.05).  Levels of T regulatory cells did not increase significantly above pretreatment levels until cycle 1 of chemotherapy (p<0.05). In patient plasma samples, elevated levels of CXCL10 at pretreatment were associated with a more favourable outcome (p<0.05).

Conclusions: Our results indicate the development of marked immunosuppression with treatment in the majority of HGG patients. Further work will determine whether immune and inflammatory changes identified can be utilised as markers of outcome in patients with HGG.