48P - Pattern of expression, transcriptional states and clinical implications of tumour-infiltrating lymphocytes (TILs) in curatively-treated cholangiocarcinoma (CCA) patients (pts): The TILBIL study

Background

Deciphering the role of the adaptive immune system is key to fully realize the potential of immuno-oncology in CCA. TILs are components of the immune microenvironment with a prognostic value across cancer types yet understudied in CCA.

Methods

Tissue blocks from 70 CCA pts undergoing radical surgery between 2013-2023 at the University Hospital of Modena were retrieved. IHC for CD4, CD8 and Foxp3 was performed for the intratumoural (i) and stromal (s) compartment. TILs were recorded as continuous variables and dichotomized to the median. Both bulk RNAseq and spatial trascriptomics were applied through TempO-seq and GeoMx. Correlation analyses and survival models were performed using IBM SPSS Statistics version 25.0.

Results

55% and 42% pts had iCD4+high and sCD4+high CCAs, 54% and 27% of them had iCD8+high and sCD8+high CCAs, and 28% and 34% of them had iFoxp3+high and sFoxp3+high CCAs. iCD4+ high CCAs were associated with pN0 status and a significantly longer RFS than CD4+ low cases (p=0.02). Contrariwise, pts with increased iCD8+ T cell density had significantly shorter RFS than iCD8+ T cells low tumours (p=0.05). iCD4+ T cells together with ECOG PS, nodal status, and adjuvant chemotherapy were independent predictors of outcome. Among iCD4+ high cases, adjuvant chemotherapy significantly prolonged survival compared to observation alone (p=0.01), while no difference was seen within the iCD4+ low subgroup (p=0.06). Compared to CCAs with lower TILs infiltration, iCD4+ high and iCD8+high subsets exhibited 342 and 393 differentially expressed genes, enriched in metabolic, beta-catenin and KRAS pathways and interferon alfa, DNA repair and VEGF networks, respectively.

Conclusions

More than 50% of CCAs displayed high intratumour infiltration of CD4+ and CD8+ TILs, which defined transcriptionally distinct entities with different clinical implications. Interestingly, higher iCD4+ density predicted a favourable prognosis and a benefit from adjuvant chemotherapy in our cohort. These preliminary findings prompt future studies diving into the biomarker potential of TILs in CCA.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Azienda Ospedaliero Universitaria di Modena.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.