Leukaemia inhibitory factor is associated with treatment resistance in oesophageal adenocarcinoma

The cover for issue 72 of Oncotarget features Figure 5A, "Elevated levels of secreted LIF negatively correlates with lymphocyte infiltration in human OAC pre-treatment biopsies," by Buckley, et al.

Inflammation influences OAC given the increased risk of cancer development and poor outcome for obese patients where altered secretion of adipokines and cytokines from adipose tissue contributes a pro-tumourigenic environment. Furthermore, significantly higher circulating levels of LIF were present in the serum from treatment-naive OAC patients who had a subsequent poor pathological response to neo-adjuvant therapy.

Dr. Jacintha O'Sullivan from the Department of Surgery, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland said, "Oesophageal cancer is the 8th most common cancer worldwide with approximately 456,000 new cases diagnosed annually."

Furthermore, OAC has been identified as an inflammatory-driven upper gastrointestinal cancer and previous studies have reported the role of inflammation as a negative regulator of response to radiation treatment in OAC. C3a and C4a, components of the complement system, were previously found to be upregulated in the pre-treatment serums of OAC patients having a subsequent poor pathological response to neo CRT, when compared to patients having a good response treatment. Differential expression of LIF and/or LIFR is reported in a number of cancers including breast cancer, colorectal cancer, NPC, osteosarcoma, pancreatic cancer, melanoma, cholangiocarcinoma and cervical cancer.

Figure 5: Elevated levels of secreted LIF negatively correlates with lymphocyte infiltration in human OAC pre-treatment biopsies. (A) CorrPlot illustrating the correlation values of secreted LIF from OAC treatment naïve biopsies cultured ex-vivo to patient clinical characteristics (stage of differentiation, tumour stage, nodal status and BMI) and percentage tumour stroma immune cell infiltrations (neutrophils, eosinophils, lymphocytes and plasma cells). Blue indicates a positive correlation, red negative correlation, (n=6)

This study aimed to investigate the association of the pro-inflammatory cytokine LIF with response to neo-adjuvant treatment in OAC, in both in-vitro settings and in pre-treatment OAC patient serum and biopsies. In-vivo, circulating LIF was significantly elevated in pre-treatment serum from OAC patients with a subsequent poor response to neo-adjuvant treatment.

The Jacintha O'Sullivan research team concluded, "In this study we have shown an association between expression of the IL-6 family member LIF and treatment response in OAC, both in-vitro cell line models, and in pre-treatment OAC patient serum and biopsies. Furthermore, given the increased secretion of LIF from our radioresistant cells following irradiation, and the tight association of secreted LIF with other pro-tumourigenic factors from our OAC patient tumours, targeting of the LIF pathway to boost treatment response warrants investigation in future studies in OAC."

Full text - https://doi.org/10.18632/oncotarget.25950

Correspondence to - Jacintha O'Sullivan - OSULLIJ4@tcd.ie

Keywords - LIF, oesophageal cancer, LIFR, treatment resistance, radiation