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Open Access 01-12-2014 | Research article

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

Authors: Elena García-Martínez, Ginés Luengo Gil, Asunción Chaves Benito, Enrique González-Billalabeitia, María Angeles Vicente Conesa, Teresa García García, Elisa García-Garre, Vicente Vicente, Francisco Ayala de la Peña

Published in: Breast Cancer Research | Issue 6/2014

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.

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Title: Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer
Authors: Elena García-Martínez
Ginés Luengo Gil
Asunción Chaves Benito
Enrique González-Billalabeitia
María Angeles Vicente Conesa
Teresa García García
Elisa García-Garre
Vicente Vicente
Francisco Ayala de la Peña
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 6/2014
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-014-0488-5

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