The relationship between the immune landscape and phenotypic subtypes in patients with colorectal cancer


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Jitwadee Inthagard1,Joanne Edwards1,Antonia Roseweir1
1University of Glasgow

Abstract

Background

With increasing interest in immunotherapy and licencing of pembrolizumab for metastatic MMR-deficient colorectal cancer (CRC), understanding the immune landscape of CRC tumours is critical. Subsequently, there is a drive to define subtypes of CRC, leading to the development of four phenotypic subtypes. Therefore, the aim of this study was to investigate the immune context of phenotypic subtypes to assess their utility as predictive markers. 

Method

Within a cohort of 1030 patient with CRC from the Greater Glasgow and Clyde NHS, immunohistochemistry was performed on a tissue microarray for CD3 and CD8 T-lymphocytes. Cell counts were performed within each 0.6um core, and ROC analysis used to define cut-offs. Cell counts were analysed for associations with cancer-specific survival (CSS) and phenotypic subtype.

Results

In the full cohort, CD3 associated with CSS both in cancer cell nests (p<0.001) and stroma (p<0.001) and was independently prognostic within the cancer cell nests (p=0.005). In the phenotypic subtypes, CD3 cancer (p=0.029) and stroma (p=0.002) were upregulated in the immune subtype.  However, only CD3 cancer significantly associated with CSS in this subtype (P=0.001). Similarly, in the full cohort, CD8 associated with CSS in both cancer cell nests (p=0.002) and stroma (p=0.003) and was independently prognostic within the cancer cell nests (p=0.016). In phenotypic subtypes, CD8 cancer (p<0.001) and stroma (p<0.001) were also upregulated in the immune subtype. Similar to CD3, only CD8 in the cancer cell nest significantly associated with CSS in this subtype (P=0.020). No association were seen with any other phenotypic subtype.

Conclusion

CD3 and CD8 T-lymphocytes are associated with good prognosis in stage I-III CRC and associate with an immune phenotypic subtype. It was interesting that within the immune subtype which has a good prognosis, T-lymphocytes can further stratify CSS. The results suggest that this subtype may be a candidate for immunotherapy.