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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, CD20 / immunology
  • Antigens, CD20 / metabolism
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology*
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / immunology*
  • Female
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis
  • Taxoids / therapeutic use
  • Trastuzumab
  • Tumor Microenvironment / immunology*
  • Young Adult

Substances

  • Anthracyclines
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antigens, CD20
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents
  • CD3 Complex
  • CD4 Antigens
  • CD68 antigen, human
  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Taxoids
  • Trastuzumab