Adenocarcinoma Contains More Immune Tolerance Regulatory T-cell Lymphocytes (Versus Squamous Carcinoma) in Non-small-Cel
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LUNG CANCER
Adenocarcinoma Contains More Immune Tolerance Regulatory T-cell Lymphocytes (Versus Squamous Carcinoma) in Non-small-Cell Lung Cancer Candice C. Black • Mary Jo Turk • Konstantin Dragnev • James R. Rigas
Received: 2 January 2013 / Accepted: 24 February 2013 / Published online: 15 March 2013 Ó Springer Science+Business Media New York 2013
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.
C. C. Black (&) Department of Pathology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA e-mail: [email protected] M. J. Turk Department of Immunology, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA K. Dragnev Department of Hematology and Oncology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA J. R. Rigas Comprehensive Thoracic Oncology Program, Norris Cotton Cancer Center, Lebanon, NH 03756, USA
Results All lymphoid tissue contains Tregs, but adenocarcinoma had significantly higher levels than both inflammatory lung controls and squamous carcinomas (p B 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. Keywords Lung cancer Adenocarcinoma Tregs Regulatory T cells FoxP3
Rudolf Virchow believed pathology stemmed from alterations of normal physiology and insufficiency of the immune regulatory apparatus [1]. Dysregulated self-immunity involves a recently recognized regulatory T lymphocyte subset (Treg) shown to play a role in self-recognition and autoimmunity. CD4 ? CD25 ? Tregs are a subset of CD4 T cells that suppress immune responses and previously referred to as suppressor T cells. Tregs account for 5–15 % of CD4
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