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Adenocarcinoma Contains More Immune Tolerance Regulatory T-cell Lymphocytes (Versus Squamous Carcinoma) in Non-small-Cell Lung Cancer

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Abstract

Background

Regulatory T lymphocytes (Tregs) are known to have host-immune dampening effects in many tumors and to be associated with increased tumor recurrence. Pharmacologic therapies have been developed to target these cells and hence strengthen the host’s immune system. The FoxP3 gene is a marker of Tregs and can be visualized with immunohistochemistry (IHC). We investigated the presence and pattern of Tregs in non-small-cell lung tumors to determine possible therapeutic targets in lung cancer.

Methods

We selected archival samples of primary lung carcinoma and benign inflamed lung from 32 surgical resections. We created a tissue array containing duplicate cores from the N1 and N2 nodal stations from 16 of the cases along with paired benign lung and tumor. We used whole-slide analysis for the other 16 cases. We used FoxP3 IHC to visualize Tregs in all lymphoid tissue present and to assess the quantity and pattern within the tissues.

Results

All lymphoid tissue contains Tregs, but adenocarcinoma had significantly higher levels than both inflammatory lung controls and squamous carcinomas (p ≤ 0.008). Benign N1 lymph nodes (from patients with lung cancer) showed higher numbers of Tregs for adenocarcinoma versus squamous carcinoma.

Conclusions

These findings reveal that Tregs are present in all lung tissues examined, but with significant enrichment in adenocarcinoma. This may lead to a more permissive microenvironment for adenocarcinoma and may explain aggressive patterns of tumor spread for this histology. Lung cancer patients with adenocarcinoma histology may benefit most from Treg-targeted therapy.

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA

    Candice C. Black

  2. Department of Immunology, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH, 03756, USA

    Mary Jo Turk

  3. Department of Hematology and Oncology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH, 03756, USA

    Konstantin Dragnev

  4. Comprehensive Thoracic Oncology Program, Norris Cotton Cancer Center, Lebanon, NH, 03756, USA

    James R. Rigas

Authors
  1. Candice C. Black
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  2. Mary Jo Turk
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  3. Konstantin Dragnev
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  4. James R. Rigas
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Correspondence to Candice C. Black.

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Black, C.C., Turk, M.J., Dragnev, K. et al. Adenocarcinoma Contains More Immune Tolerance Regulatory T-cell Lymphocytes (Versus Squamous Carcinoma) in Non-small-Cell Lung Cancer. Lung 191, 265–270 (2013). https://doi.org/10.1007/s00408-013-9455-7

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  • DOI: https://doi.org/10.1007/s00408-013-9455-7

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