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In situ cytokine production by breast cancer tumor-infiltrating lymphocytes

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Abstract

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.

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Authors and Affiliations

  1. From the Department of Surgery, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, New Hampshire, USA

    Benjamin J. Camp MD &  Richard J. Barth Jr MD

  2. the Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, New Hampshire, USA

    Vincent A. Memoli MD

  3. the Department of Community and Family Medicine, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, New Hampshire, USA

    Leila A. Mott MS

  4. the Department of Biology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, New Hampshire, USA

    Sonya T. Dyhrman BA

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  1. Benjamin J. Camp MD
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  3. Vincent A. Memoli MD
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  5. Richard J. Barth Jr MD
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Camp, B.J., Dyhrman, S.T., Memoli, V.A. et al. In situ cytokine production by breast cancer tumor-infiltrating lymphocytes. Annals of Surgical Oncology 3, 176–184 (1996). https://doi.org/10.1007/BF02305798

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  • DOI: https://doi.org/10.1007/BF02305798

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