E-Poster Presentation 33rd Lorne Cancer Conference 2021

ASSESSMENT OF THE IMMUNE MICROENVIRONMENT IN OESOPHAGEAL CANCER REVEALS A POTENTIAL PROGNOSTIC ROLE FOR TUMOUR INFILTRATING NEUTROPHILS (#156)

Carlos S Cabalag 1 2 , Owen Prall 1 , John Ciciulla 3 , Laurence Galea 3 , Niko Thio 1 , Paul J Neeson 1 , Gisela Mir Arnau 1 , Cuong P Duong 1 2 , Nicholas J Clemons 1 2 , Wayne A Phillips 1 2 4
  1. Peter MacCallum Cancer Centre, Melbourne, VICTORIA, Australia
  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
  3. Anatomical Pathology Department, Melbourne Pathology, Melbourne, Victoria, Australia
  4. Department of Surgery - St. Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia

Background: Significant advances have been made in our understanding of tumour infiltrating lymphocytes (TILs) and immune microenvironment, leading to the adoption of immune checkpoint blockade as another pillar of cancer treatment.  Nevertheless, response to immune checkpoint blockade in oesophageal cancer (OC) remains poor and non-durable.  Thus, in order to understand the mechanisms of resistance, the aim of this study was to assess the immune microenvironment in oesophageal cancer with respect to TILs, tumour infiltrating neutrophils (TIN), the expression of immune related genes, and their association with treatment response and prognosis.

Methodology:  Study cohort consisted of 58 OC patients who had neoadjuvant chemoradiotherapy (CRT) followed by surgical resection.  TILs and TINs were quantified in separate compartments (tumour/stroma/scar) of pre-treatment and surgical resection specimens, expressed as the percentage area infiltrated1.  RNA was extracted from sections where TILs and TINs were quantified and gene expression was assessed using the Nanostring Platform based on the PanCancer Immune Profiling Panel.

Results:  For patients who had low (< 10% area) pre-treatment TIL counts, an increase in TIL count after CRT was associated with a superior progression free survival (p < 0.01).  Post-CRT TIL infiltration counts were not prognostic of overall or disease specific survival.  In the entire cohort, the presence of TINs in post-treatment surgical resection specimens was independently associated with poor disease specific survival (HR 2.88; 1.32 – 6.25; p < 0.01).  In neutrophil-infiltrated tumours, differential gene expression analysis reveals a higher expression of CXCL5 and immune checkpoint molecules CTLA4 and TIM3. 

Conclusion:  The degree of TIL infiltration in the tumour microenvironment is not prognostic in OC.  TINs were found to be an independent adverse prognostic factor in patients who have undergone neoadjuvant CRT.   Our study also shows that the presence of TINs is associated with the overexpression of CXCL5, a putative neutrophil chemotactic factor with pro-tumoural effects.  Collectively, our results suggest that TINs in OC may contribute to treatment resistance and progressive disease.