In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 3_suppl ( 2015-01-20), p. 602-602
Abstract:
602 Background: We previously reported that an adaptive Th1 immune response (CD3/CD8/CD45RO T-cells) observed in resected primary colorectal tumor and liver colorectal metastases (LCM) is an important prognostic factor. B and FoxP3 regulatory lymphocytes participate to the modulation of this response. We aimed to investigate whether the preoperative treatments influenced the quality and the density of the immune infiltrates previously reported in the LCM. Methods: We used a cohort of metastatic colorectal patients (n=107) engaged for curative liver surgery with available FFPE blocks for all resected LCM to confirm the prognostic impact of the immune response. Among this cohort of 338 LCMs, 46 were completely resected after chemotherapy (CT) alone, 130 after CT + anti-VEGF, 118 after CT + anti-EGFR and 44 after surgery alone. LCMs were analyzed for histological response according the Tumor Regression Grade (TRG) and regrouped as Response (R, TRG1-3) or No Response (NR, TRG4-5). 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 LCM 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: LCMs showing R (compared to NR and untreated LCM) were more frequently associated with a high immune infiltrate for CD3+ (CT: p 〈 0.005; IM: p 〈 0.05), CD8+ (CT: p 〈 0.005; IM: p 〈 0.005) and CD20+ (CT: p 〈 0.05). Conversely, high FoxP3+ density in the CT and IM was related to NR and untreated LCMs (p 〈 0.01). LCMs treated with an anti-EGFR therapy showed higher densities of CD3+ (CT: p 〈 0.005; IM: p 〈 0.01), CD8+ (CT: p 〈 0.005), CD45RO+ (CT: p 〈 0.005), CD20+ (CT: p 〈 0.005) and FoxP3+ (CT: p 〈 0.05; IM: p 〈 0.005) compared to other treatments and untreated LCMs. Conclusions: Preoperative treatment modifies the LCM immune microenvironnement. LCMs with a histological response show a cytotoxic immune response (CD3+/CD8+) with associated B-cells (CD20+) and downregulated Tregs (FoxP3+). The use of an anti-EGFR therapy significantly increases immune infiltration in the CT.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2015.33.3_suppl.602
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2015
detail.hit.zdb_id:
2005181-5
