Cancer Antigen Presentation in Colorectal Cancer Local Metastases


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Thomas Starkey1,Thomas Starkey1,Tessa Sanberg2,Roland Arnold1,Ian Tomlinson1,Lennard Lee1
1University of Birmingham,2Universiteit Leiden

Abstract

Background

The induction of acquired immunity requires the coordinated interplay between cells of the innate system and naïve lymphocytes and this occurs in the draining lymph nodes of tumours. Lymph node metastases represent an unusual immune phenomenon whereby tumours are able to persist in close proximity to antigen presenting cells. We sought to understand how cancer antigen presentation is altered in lymph node metastases, whether there is a failure of cancer antigen presentation enabling lymph node metastasis or whether the lymph node continues to be a site by which acquired immunity is promoted and an anti-tumour response propagated.

Method

296 resection specimens from 148 stage III colorectal cancer patients was assembled. RNA sequencing was performed on the LNMTD and primary tumour. Batch effect, normalisation, differential expression was performed. Antigen presentation and checkpoint activation was determined using genesets from “Reactome” and published literature. 

Results

Lymph node metastases are associated with significance differences in cancer antigen presentation. Both MHC class 1 and MHC 2 antigen presentation were significantly upregulated with a more pronouced effect for the MHC class II geneset. In the lymph node metastases, cell lineage analysis identified there was upregulation of genes associated with increased levels of dendritic cells and B cells. There was no increase in the macrophages gene set.

Conclusion

During metastasis, the immune environment promoted by the tumour is altered. We are able to identify the upregulation of MHC antigen presentation. This effect was not dependent on macrophages, but likey due to increased dendritic and B cells. We believe our results suggest that colorectal cancer lymph node metastases does not arise through a failure of cancer antigen-presentation, but actually results in increased antigen presentation and potentially enhanced immunoediting at this site.