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
  • 1Medical Oncology, Leiden University Medical Center, 2333 ZA - Leiden/NL
  • 2Medical Oncology / Surgery, Leiden University Medical Center, 2333 ZA - Leiden/NL
  • 3Surgery, Leiden University Medical Center, 2333 ZA - Leiden/NL
  • 4Pathology, Leiden University Medical Center, 2333 ZA - Leiden/NL
  • 5Statistics, Leiden University Medical Center, 2333 ZA - Leiden/NL



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).


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).


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.


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


Dutch Cancer Society, Amgen, Novartis, Sanofi


J.W.R. Nortier, J.R. Kroep: Research grant Novartis, Amgen and Sanofi. All other authors have declared no conflicts of interest.