554P - B cells (CD20+) associated to tumor infiltrating cytotoxic T-cells observed on resected liver colorectal metastases (LCM) are prognostic

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Marc van den Eynde
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors M. van den Eynde1, B. Mlecnik2, J. Machiels3, D. Debetancourt1, A. Jouret-Mourin4, C. Sempoux5, J. Gigot6, C. Hubert7, Y. Humblet8, N. Haicheur9, F. Marliot9, F. Pagès9, J. Galon2
  • 1Medical Oncology, Cliniques universitaires St-Luc, 1200 - Brussels/BE
  • 2Inserm Team 15, Centre de Recherche des Cordeliers, 75006 - Paris/FR
  • 3Medical Oncology, Cliniques Universitaires St. Luc, 01200 - Brussels/BE
  • 4Pathology Department, Cliniques universitaires St-Luc, 1200 - Brussels/BE
  • 5Pathology, Cliniques universitaires St-Luc, 1200 - Brussels/BE
  • 6Surgery, Cliniques universitaires St-Luc, 1200 - Brussels/BE
  • 7Digestive Surgery, Cliniques universitaires St-Luc, 1200 - Brussels/BE
  • 8Medical Oncology Dept, Cliniques Universitaires St. Luc, BE-1200 - Brussels/BE
  • 9Immunology, Hopital Europen Georges Pompidou, 75908 - Paris/FR

Abstract

Aim

Colorectal cancer infiltrating cytotoxic T-cells (CD8+ cells) are a strong prognostic factor for survival after primary tumor and metastases resection. The impact of B cells for prognosis is less characterized.

Methods

Metastatic colorectal patients (pts) engaged for curative liver surgery with available FFPE blocks for all resected LCM, were included. The density of CD8+ and CD20+ cells in the metastasis (CT) and the invasive margin (IM) for all LCM was determined by whole-slide immunohistochemistry and quantified with dedicated image analysis software. The mean value of the 3 most infiltrated areas (0.8 mm2) was calculated. The densities of CD8 and CD20 (CT and IM regions) were classified into Hi or Lo according to cut-off values (minimal p-value approach). The total number of Hi densities was calculated to determine the immunoscore (IS) 0-2 Hi (low IS) or 3-4 Hi (high IS). For pts with multiple LCM, all LCM were quantified. The mean value of all densities, the least and the most infiltrated LCM/pt were analyzed. Cumulative DFS/OS analyses were performed using the Kaplan-Meier estimator. The hazard ratio (HR) for OS/DFS comparing (IS0-2 vs 3-4) was determined using univariate Cox regression and the significance by log-rank tests.

Results

294 LCM from 88 patients (M/F 1.1, mean 3.3/pt, synchr/metachr 5.8) were included. For the least infiltrated metastasis: a high IS is prognostic for DFS and OS. Independently of CD8 cells, a high CD20 density associated concomitantly with both regions (CT/IM) is prognostic for OS (HR: 0.36; p = 0.00004) but not for DFS (HR 0.58, p = 0.1).

LCM/patient IS Survival HR Logrank
(IS0-2 vs 3-4; 95%IC) p-value
Mean of all CD8-CD20 DFS 0.44 (0.22-0.91) 0.5
OS 0.29 (0.09-1.00) 0.03
Less of all CD8-CD20 DFS 0.31 (0.18-0.53) 0.0005
OS 0.25 (0.12-0.51) 0.00003
Most of all CD8-CD20 DFS 0.92 (0.53-1.56) 0.7
OS 0.95 (0.42-2.12) 0.9

Conclusions

B cells (CD20+) associated with cytotoxic T cells (CD8+) in both tumor regions (CT/IM) of the least infiltrated LCM/pt are highly prognostic after curative resection. These results confirm the important role of tumor regions and of B-cells (CD20+) for the tumor immune response.

Disclosure

All authors have declared no conflicts of interest.