Annals of Surgical Oncology

, Volume 3, Issue 2, pp 176–184 | Cite as

In situ cytokine production by breast cancer tumor-infiltrating lymphocytes

  • Benjamin J. Camp
  • Sonya T. Dyhrman
  • Vincent A. Memoli
  • Leila A. Mott
  • Richard J. BarthJr
Original Articles


Background: Human breast cancers progressively grow despite the presence of extensive lymphocytic infiltration and specific antitumor immune recognition, thereby calling into question the competency of breast tumor-infiltrating lymphocytes (TIL). The function of breast TILs in vivo and their possible role in the suppression of an antitumor immune response are largely unknown.

Methods: The cytokines produced in situ by lymphocytes in 89 breast carcinomas and 14 benign breast lesions were assessed using immunohistochemistry.

Results: The majority of tumor and benign breast samples contained T-cell infiltrates, which were disclosed using an anti-CD3 antibody stain. The percentage of tumor samples in which ⩾3% of the lymphocytes were producing cytokines was as follows: interleukin (IL)-2 45%, IL-4 36%, tumor necrosis factor-alpha (TNF-α) 28%, transforming growth factor-beta 1 (TGF-β1) 20%, IL-10 11%, interferon-gamma (IFN-γ) 4%, and granulocytemacrophage colony-stimulating factor (GM-CSF) 3%. Production of IL-2, IL-4, and TGF-β1 by TILs in breast cancers exceeded that detected in benign breast lesions (p<0.005). Significantly more tumor samples contained lymphocytes producing IL-2, IL-4, TGF-β1, and TNF-α than IFN-γ and GM-CSF (p<0.002 for each comparison). One or more of the potentially immunoinhibitory cytokines—IL-4, IL-10, or TGF-β1—were produced by lymphocytes in 44% of the specimens. No significant associations were seen between lymphocyte production of a particular cytokine and disease-free survival (median follow-up 43 months).

Conclusions: Immunohistochemical techniques can be used to detect cytokine secretion by TILs in preserved tissue. The relative lack of secretion of IFN-γ and GM-CSF, rather than a deficiency of IL-2, may explain why the antitumor immune response to breast cancer is impaired.

Key Words

Breast cancer Tumor-infiltrating lymphocyte Immunohistochemistry Interleukin-2 Interleukin-4 Tumor growth factor-beta 1 


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Copyright information

© The Society of Surgical Oncology, Inc. 1996

Authors and Affiliations

  • Benjamin J. Camp
    • 1
  • Sonya T. Dyhrman
    • 4
  • Vincent A. Memoli
    • 2
  • Leila A. Mott
    • 3
  • Richard J. BarthJr
    • 1
  1. 1.From the Department of SurgeryDartmouth-Hitchcock Medical Center and Norris Cotton Cancer CenterLebanonUSA
  2. 2.the Department of PathologyDartmouth-Hitchcock Medical Center and Norris Cotton Cancer CenterLebanonUSA
  3. 3.the Department of Community and Family MedicineDartmouth-Hitchcock Medical Center and Norris Cotton Cancer CenterLebanonUSA
  4. 4.the Department of BiologyDartmouth-Hitchcock Medical Center and Norris Cotton Cancer CenterLebanonUSA

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