SP5.1.11 The immune landscape of the Tumour draining lymph node and the Tumour Microenvironment in oesophageal; A novel therapeutic target. (28th October 2021) - Donlon, Noel
Abstract: Aim: The tumour microenvironment (TME) and tumour-draining lymph node microenvironment (LNME) remain poorly understood. Our study profiles the immune, angiogenic and inflammatory environment of the LNME and the TME of oesophagogastric patients. Methods: The prognositc value of nodal status, clinical stage and tumour regression grade (TRG) was evaluated using a cohort of OAC patients (n = 702). Immune checkpoints (ICs) on tumour-draining lymph nodes(TDLNs, n = 6) and tumour tissue(n = 9) at surgical resection was assessed by flow cytometry. We also screened for cytokines, angiogenic mediators and chemokines. Using The Cancer Genome Atlas (TCGA), protein and mRNA levels (n = 72) and mutated versus non-mutated copies(n = 87) of this panel was correlated with survival. Results: The frequency of CD3+TIM-3 and PD-1+T cells in TDLNs positively correlated with clinical tumour status as did CD8 + PD-1+TIGIT + T cells with nodal burden. Pro-angiogenic factor bFGF was significantly higher within the TME compared with the LNME. PIGF and SAA mediators of tumour growth were significantly higher in the LNME and levels of SAA in LNME positively correlated with adverse features. High levels of pro inflammatory IL-8, IL-6 and Flt1, mutations in pro-inflammatory genes CCL26, IL-31 and IL-17C and anti-tumour IL-1RN and CCL22 correlated with reduced overall survival. Conclusions: The TME is more immunosuppressive than the TDLN, however, certain pro-angiogenic factors were enriched in TDLNs suggesting the priming of a pre-metastatic niche. Given the association of ICs with clinical features and tumour biology this may help to inform novel therapeutic approaches.