31P - Tumor-infiltrating lymphocytes, tumor-associated macrophages and HLA class 1 expression in breast cancer patients treated with neoadjuvant chemothe...
| Date | 08 December 2017 |
| Event | ESMO Immuno-Oncology Congress 2017 |
| Session | Lunch & Poster Display session |
| Topics | Complications of Treatment Cancer Immunology and Immunotherapy Head and Neck Cancers |
| Presenter | Anne de Groot |
| Citation | Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711 |
| Authors |
A.F. de Groot1, E.J. Blok2, A. Charehbili2, C.C. Engels3, V.T.H.B.M. Smit4, N.G. Dekker-Ensink3, H. Putter5, C.J.H. van de Velde3, G. Liefers3, J.W.R. Nortier1, P.J.K. Kuppen3, S.H. van der Burg1, J.R. Kroep1
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Abstract
Background
Tumor-infiltrating lymphocytes (TILs) are associated with pathological complete response (pCR) and survival after neoadjuvant chemotherapy in early breast cancer. Studies on the impact of tumor-associated macrophages (TAMs) or antigen HLA class 1 (HLA-1) expression in this context, however, are limited. Therefore, we investigated their prognostic and predictive role in relation to neoadjuvant chemotherapy with or without zoledronic acid (NEOZOTAC trial).
Methods
On baseline tumor biopsies of the NEOZOTAC patients, immunohistochemical stainings were performed for CD8 (cytotoxic T-cells), FoxP3 (regulatory T-cells), CD68 (macrophages) and for HLA class 1 (HLA-1): HLA-A (HCA2) and HLA-B/C (HC10). Markers were associated with pCR and disease-free survival (DFS).
Results
Patients with strong (above median) intratumoral CD8+ infiltration (pCR: 18.4% vs. 5.2%; p = 0.011) or expression of HLA-1 (≥5% of tumor cells expressing HLA-A or HLA-B/C; pCR: 14.2% vs. 3.4%; p = 0.031) displayed a higher pCR rate compared to the other patients. The presence of HLA-1 expression was a requirement for a pCR when tumors were CD8+ infiltrated (pCR: 21.8% vs. 6.7%; p = 0.035) as they had no impact when HLA-1 expression was downregulated (pCR: 5.9% vs. 0%; p = 0.194). There was no direct association between CD8+, FoxP3+, CD68+ or HLA-1 expression status and DFS, however, patients with a strong CD8+ infiltrated tumor displayed a better DFS when tumors expressed HLA-1 (HR: 0.41, 95% CI 0.15-1.10, p = 0.08). More in depth analyses (e.g. on marker ratio’s and the effect of CD68+ and Foxp3+ infiltrate in HLA-1 expressing tumors) are awaited and will be available before the meeting.
Conclusions
A strong infiltration with CD8+ cells and expression of HLA-1 is associated with a higher pCR rate and better DFS after neoadjuvant chemotherapy.
Clinical trial identification
EudraCT number 2009-016932-11 NL30600.058.09 NCT01099436
Legal entity responsible for the study
Leiden University Medical Center
Funding
Dutch Cancer Society, Amgen, Novartis, Sanofi
Disclosure
J.W.R. Nortier, J.R. Kroep: Research grant Novartis, Amgen and Sanofi. All other authors have declared no conflicts of interest.