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Poster display session

1744 - High PD-L1 expression and high CD8+ T-cell infiltration identifies a new subpopulation of colorectal cancer with high risk of relapse and poor outcome

Date

09 Sep 2017

Session

Poster display session

Presenters

Marwan Fakih

Citation

Annals of Oncology (2017) 28 (suppl_5): v158-v208. 10.1093/annonc/mdx393

Authors

M. Fakih1, C. Ouyang2, C. Wang3, T.Y. Tu3, M. Cho1, M. Sy1, J. Longmate4, P.P. Lee3

Author affiliations

  • 1 Medical Oncology, City of Hope, 91010 - Duarte/US
  • 2 Office Of Chief Informatics, City of Hope, 91010 - Duarte/US
  • 3 Immuno-oncology Bri, City of Hope, 91010 - Duarte/US
  • 4 Information Sciences - Bri, City of Hope, 91010 - Duarte/US
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Resources

Abstract 1744

Background

CD8+ T-cell primary tumor infiltration is associated with improved colorectal cancer (CRC) outcome. However, the interaction between CD8+ T-cell infiltration and intra-tumor PD-L1 expression has not been previously characterized. This study aims to explore the impact of PD-L1 expression and degree of CD8+ T-cell infiltration on the outcome of patients with stage II and III CRC.

Methods

CD8, PD-1, PD-L1, cytokeratin 20, and CD68 expression were quantified via multi-spectral immunohistochemistry of primary CRC tumors from 35 patients with recurrent disease (cases) and 36 patients without recurrence (controls). The TCGA (The Cancer Genome Atlas) and the NCBI-GEO (Gene Expression Omnibus) datasets of 385 and 828 stage II-III cases, respectively, were used to validate the prognostic value of the discovery set biomarkers, both for relapse free survival (RFS) and overall survival (OS).

Results

In the 71-patient discovery case-control set, densities of CD8+ and PD-L1+ cells in tumor microenvironment classified patients into three distinct populations. High CD8+ cell infiltration (above median) and high PD-L1 expression (>90 percentile) was associated with high risk of relapse: all 7/7 patients with CD8Hi/PD-L1Hi experienced disease relapse, despite being enriched in mismatch repair deficiency (4 patients). Low CD8+ cell infiltration was associated with a high relapse rate irrespective of PD-L1 status: 80% of patients with CD8L relapsed. CD8Hi in the absence of high PD-L1 expression (CD8Hi/PD-L1L) had the lowest risk of relapse: 7% of patients relapsed. The validation data sets confirmed that the CD8Hi/PD-L1L and the CD8L groups carried an inferior RFS (NCBI-GEO data set: HR = 1.655, p = 0.02) and OS (TCGA data set: HR = 3.556, p = 0.0095) in comparison to the CD8Hi/PD-L1L group. A multivariate analysis that includes age, stage, and mismatch repair (MMR) status, confirmed the independent impact of both CD8Hi and PD-L1Hi on RFS and OS in both validation sets.

Conclusions

CD8Hi/PD-L1Hi defines 10% of patients with stage II/III CRC and confers a high risk of relapse, despite enrichment with MMR deficiency. This subgroup of patients may be suitable for the investigation of PD-1 checkpoint inhibitors.

Clinical trial identification

Not applicable

Legal entity responsible for the study

City of Hope

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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