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Breast Cancer Res. 2014 Nov 29;16(6):488. doi: 10.1186/s13058-014-0488-5.

Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer.

Author information

1
Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. helenagarciam@gmail.com.
2
Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. gines.luengo@um.es.
3
Department of Pathology, University Hospital Morales Meseguer, Murcia, Spain. mariaa.chaves@carm.es.
4
Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. engonbil@um.es.
5
Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. marianvico@yahoo.es.
6
Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. tggarc@gmail.com.
7
Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. eliggarre3@gmail.com.
8
Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. vvg@um.es.
9
Centro Regional de Hemodonación, Murcia, Spain. vvg@um.es.
10
Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain. frayala@um.es.

Abstract

INTRODUCTION:

Tumor microenvironment immunity is associated with breast cancer outcome. A high lymphocytic infiltration has been associated with response to neoadjuvant chemotherapy, but the contribution to response and prognosis of immune cell subpopulations profiles in both pre-treated and post-treatment residual tumor is still unclear.

METHODS:

We analyzed pre- and post-treatment tumor-infiltrating immune cells (CD3, CD4, CD8, CD20, CD68, Foxp3) by immunohistochemistry in a series of 121 breast cancer patients homogeneously treated with neoadjuvant chemotherapy. Immune cell profiles were analyzed and correlated with response and survival.

RESULTS:

We identified three tumor-infiltrating immune cell profiles, which were able to predict pathological complete response (pCR) to neoadjuvant chemotherapy (cluster B: 58%, versus clusters A and C: 7%). A higher infiltration by CD4 lymphocytes was the main factor explaining the occurrence of pCR, and this association was validated in six public genomic datasets. A higher chemotherapy effect on lymphocytic infiltration, including an inversion of CD4/CD8 ratio, was associated with pCR and with better prognosis. Analysis of the immune infiltrate in post-chemotherapy residual tumor identified a profile (cluster Y), mainly characterized by high CD3 and CD68 infiltration, with a worse disease free survival.

CONCLUSIONS:

Breast cancer immune cell subpopulation profiles, determined by immunohistochemistry-based computerized analysis, identify groups of patients characterized by high response (in the pre-treatment setting) and poor prognosis (in the post-treatment setting). Further understanding of the mechanisms underlying the distribution of immune cells and their changes after chemotherapy may contribute to the development of new immune-targeted therapies for breast cancer.

PMID:
25432519
PMCID:
PMC4303200
DOI:
10.1186/s13058-014-0488-5
[Indexed for MEDLINE]
Free PMC Article

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