Characterization of the immune microenvironment of synchronous primary tumor and liver colorectal metastases
(2015) 2015 ASCO Annual Meeting — Location: (United States) Chicago, IL (29.May.2015)
Files
No attached file found for this publication.
Details
- Authors
- Abstract
- Background: The adaptive Th1 immune response (CD3, CD8, CD45RO T cells) observed in resected primary colorectal tumor (PCT) and liver colorectal metastases (LCM) is an important prognostic factor. Preoperative treatment modifies the LCM immune microenvironment with a significant association between pathological response and increase of T (CD3, CD8) and B cells (CD20) and downregulated T regulatory cells (FoxP3). We investigated the impact of different preoperative treatments on the quality and density of the immune infiltrates in synchronous resected PCT and LCM. Methods: Metastatic colorectal patients (n = 107) undergoing curative liver surgery for all resected LCM (n = 338) were investigated. 28 patients have been operated concomitantly for synchronous LCM (n = 102) and PCT (n = 23 available) after surgery alone (S), chemotherapy (Cht) alone, Cht + anti-VEGF and Cht + anti-EGFR. The density of CD3 (T cells), CD8 (cytotoxic), CD45RO (memory), CD20 (B cells) and FoxP3 (regulatory) in the core (CT) and invasive margin (IM) of all synchronous LCM and PCT was quantified on immunostained slides. The mean density value (CT, IM) was calculated for each marker with a dedicated image analysis software on whole-slide imaging. Comparisons were made using the Wilcoxon-Mann-Whitney test. Results: Global analysis of immune cell density in LCM and corresponding PCT showed no significant correlation even when further subcategorizing by treatment (preoperative or S), metastasic burden or subdividing by the least, the mean or the highest infiltrated LCM for patients with multiple LCM.Compared to PCT, LCM were more frequently associated with a high immune infiltrate for CD3 and CD45RO in the IM (p < 0.001) and CD8 in CT and IM (p < 0.001). Conversely, high CD20 and FoxP3 density were higher in the CT of PCT (p < 0.005). When comparing preoperative treatment to S, only Cht+anti-EGFR significantly increases CD3 and CD8 in CT of LCM but not PCT (p < 0.001). Conclusions: Cytotoxic/memory T cells and B/regulatory T cell densities were significantly higher in LCM and PCT, respectively. Only anti-EGFR treatment increases T cells densities in the CT of the LCM but not in the PCT, suggesting a specific treatment effect in this tumor region.
- Affiliations
Citations
Van den Eynde, M., Mlecnik, B., Machiels, J.-P., Debetancourt, D., Bindea, G., Mourin, A., Sempoux, C., Carrasco, J., Gigot, J.-F., Hubert, C., Humblet, Y., Haicheur, N., Marliot, F., Pages, F., & Galon, J. (2015). Characterization of the immune microenvironment of synchronous primary tumor and liver colorectal metastases. Journal of Clinical Oncology, 33, 3610. https://hdl.handle.net/2078.5/174955 (Original work published 2015)