Abstract 483P
Background
Tumour-derived antigens lead to immune activation such as germinal centre (GermC) hyperplasia in regional tumour-draining lymph nodes (LNs). Thus, LN microarchitecture might provide clinically useful insights into the host’s anti-tumour immune response. It is unclear whether different neoadjuvant chemotherapy (NAC) regimens result in different immunologic responses in LNs.
Methods
GermC microarchitecture (total GermC count, absolute GermC area, %area occupied by GermC (coverage), GermC density, GermC concavity) and LN size were analysed in Haematoxylin/Eosin stained tissue sections of tumour-negative LNs (LNneg) from 643 OE05 trial patients with resectable oesophagogastric cancer after NAC (2 cycles cisplatin/fluorouracil (CF) n=333; 4 cycles epirubicin/cisplatin/capecitabine (ECX) n=310) using a multi-scale U-Net deep learning model. The relationship with treatment and clinicopathological parameters was investigated.
Results
GermC counts, coverage and density were higher in LNneg post-CF NAC compared to post-ECX NAC (all p<0.001). LNneg size and other GermC microarchitecture features did not differ between treatment arms. GermC microarchitecture was not related to any of the clinicopathological parameters.
Conclusions
This is the first study to compare GermC microarchitecture in LNneg of oesophagogastric cancer patients treated with either 2 cycles CF-NAC or 4 cycles ECX-NAC providing insights into the immune-modulating effect of different chemotherapy regimens. Our results suggest that intensified NAC may lead to depletion of GermC potentially impacting on the locoregional host’s anti-tumour immune response. Validation of our results in a second independent series is needed. Further studies should investigate the relationship between GermC microarchitecture, patient prognosis and response to adjuvant therapy, particularly immunotherapy as well as the underlying biology by comprehensive phenotyping of the LNneg immune cell populations.
Clinical trial identification
NCT00041262; ISRCTN 01852072.
Legal entity responsible for the study
The authors.
Funding
Cancer Research UK and Medical Research Council Clinical Trials Unit at University College London.
Disclosure
D.R. Magee: Other, Other: supported in part by the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Center, is a director of HeteroGenius Limited. M.G. Nankivell: Other, Other: Cancer research UK. R.E. Langley: Other, Other: Cancer research UK. D. Cunningham: Other, Other: Grants from Amgen, AstraZeneca, Bayer, Celgene, Merrimack, Medimmune, Merck Serono, Sanofi, Clovis, Eli Lilly, 4SC, Celgene, Leap and Roche, The National Institute of Health Biomedical Centre at the Institute of Research and Royal Marsden Hospital. H.I. Grabsch: Other, Other: Cancer research UK, National Institute for Health and Care Research (NIHR) Leeds Leeds Biomedical Research Center, Honoraria from AstraZeneca and BMS for scientific advisory board activities not related to the current study. All other authors have declared no conflicts of interest.