Abstract 30P
Background
MMRd CRCs are immunogenic and have a relatively good prognosis after resection. Better biomarkers to predict which tumours recur are needed.
Methods
77 resected stage 1-3 (15.6%, 53.2% and 31.2%) MMRd CRC from the TRACC trial (NCT04050345, data extract: 18/03/2024) were stained by IHC for B2M, CDX2, CD8 T cell infiltrates and PDL1. The CD8 T cell fraction was calculated at the tumour centre (TC) and invasive margin (IM). Associations with tumour stage and 24mo recurrence free survival (RFS) were evaluated.
Results
B2M expression in cancer cells was absent in 14.3% of tumours and CDX2 in 15.6%. 13.0% tumours had a PDL1 tumour proportion score (TPS) >1 and 32.5% a PDL1 combined positive score (CPS) >5. The proportion of CRCs with PDL1 TPS >1 and of CDX2 loss continuously increased and PDL1 CPS >5 continuously decreased with higher tumour stage. There was no numerical association of B2M loss or of CD8 T cell densities at the TC or IM with stage. The median follow-up was 47.8mo (IQR: 20.4-51.6mo). Patients with PDL1 TPS >1 CRCs had significantly shorter RFS (Log rank p=0.045). A non-significant trend for better RFS was seen in patients with B2M loss and a trend for worse RFS in patients with CDX2-negative CRCs. There was no association of CD8 T cells at the TC or IM with RFS. CDX2 loss was significantly associated with higher PDL1 TPS (p<0.001) and with higher CD8 T cell densities at the IM (p=0.010). PDL1 TPS >1 was associated with higher CD8 T cell densities in the TC and at the IM (p=0.034 and p=0.011), whereas PDL1 CPS >5 was associated with higher CD8 T-cell densities in the TC (p<0.001).
Conclusions
PDL1 TPS >1 was significantly associated with shorter RFS. CDX2 loss and B2M loss may be additional markers of poor and good prognosis, respectively. However, CDX2 loss is significantly associated with higher PDL1 TPS and they may hence identify similar subgroups. The low frequency of recurrences was a limiting factor. Our results indicate that PDL1 TPS >1 and the associated CDX2 loss should be further investigated in larger cohorts as biomarkers to identify MMRd CRCs with a high recurrence risk. Whether these predict benefit from adjuvant therapy with immune checkpoint inhibitors should be assessed in ongoing clinical trials.
Clinical trial identification
NCT04050345.
Legal entity responsible for the study
The Royal Marsden Hospital (Sponsor).
Funding
The Pathological Society of Great Britain & Ireland.
Disclosure
All authors have declared no conflicts of interest.