Tumor-infiltrating Immune Cell Profiles and Their Change After Neoadjuvant Chemotherapy Predict Response and Prognosis of Breast Cancer

Overview

Journal Breast Cancer Res

Specialty Oncology

Date 2014 Nov 30

PMID 25432519

Citations 139

Authors

Elena Garcia-Martinez

Gines Luengo Gil

Asuncion Chaves Benito

Enrique Gonzalez-Billalabeitia

Maria Angeles Vicente Conesa

Teresa Garcia Garcia

Elisa Garcia-Garre

Vicente Vicente

Francisco Ayala de la Pena

Affiliations

Soon will be listed here.

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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