Breast Cancer Research and Treatment

, Volume 156, Issue 2, pp 237–247 | Cite as

Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer

  • Hirofumi Matsumoto
  • Aye Aye Thike
  • Huihua Li
  • Joe Yeong
  • Si-lin Koo
  • Rebecca Alexandra Dent
  • Puay Hoon Tan
  • Jabed IqbalEmail author
Preclinical study


Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan–Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 high CD8 high CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 high CD8 high iTILs and sTILs are independent prognostic factors in TNBC.


CD4 CD8 Triple-negative breast cancer (TNBC) Lymphocytes Overall survival 



This study is a part of a research project approved by the SingHealth Centralised Institutional Review Board (CIRB Ref: 2013/664/F) and was funded by the Stratified Medicine Programme Office (Grant No: SMPO201302].

Compliance with ethical standards

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Hirofumi Matsumoto
    • 1
  • Aye Aye Thike
    • 2
  • Huihua Li
    • 3
  • Joe Yeong
    • 2
    • 4
  • Si-lin Koo
    • 5
  • Rebecca Alexandra Dent
    • 5
  • Puay Hoon Tan
    • 2
  • Jabed Iqbal
    • 2
    Email author
  1. 1.Department of PathologyRyukyu University HospitalOkinawaJapan
  2. 2.Department of PathologySingapore General HospitalSingaporeSingapore
  3. 3.Division of ResearchSingapore General HospitalSingaporeSingapore
  4. 4.Singapore Immunology Network, Agency of Science, Technology and ResearchSingaporeSingapore
  5. 5.Department of Medical OncologyNational Cancer CentreSingaporeSingapore

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