Foxp3 Expressing CD4⁺ CD25⁺ and CD8⁺CD28⁻ T Regulatory Cells in the Peripheral Blood of Patients with Lung Cancer and Pleural Mesothelioma

Human Immunology. Volume 67, Issues 1-2 , January-February 2006, Pages 1-12 [Link]

Federica Meloni^a, Monica Morosini^a, Nadia Solari^a, Ileana Passadore^a, Caterina Nascimbene^a, Monique Novo^a, Marco Ferrari^b, Marco Cosentino^b, Franca Marino^b, Ernesto Pozzi^a and Anna M. Fietta^a

^aDepartment of Hematological, Pneumological, and Cardiovascular Sciences, Section of Pneumology, IRCCS Policlinico San Matteo–University of Pavia, Pavia, Italy
^bDepartment of Clinical Medicine, Section of Experimental and Clinical Pharmacology, University of Insubria, Varese, Italy

Abstract

The role of T regulatory (Treg) cells in human cancer has not yet been clarified. We assessed the presence and function of CD4⁺ and CD8⁺ Treg cell subsets in the peripheral blood of patients with lung cancer (LC) and pleural mesothelioma (PM). We found a low but significant increase in the number of CD4⁺ T cells with phenotype and functional features of Treg cells in LC patients compared to normal healthy controls (NHC). Furthermore, total CD4⁺ T cells from LC patients proliferated less than cells from controls, suggesting that the increase in the CD4⁺ Treg cell pool has functional importance. LC patients also showed an expansion of the CD8⁺CD28⁻ T cell subset and these cells expressed Foxp3 mRNA, as recently observed in alloantigen-specific CD8⁺CD28⁻ T suppressor cells. No variation of peripheral Treg cell subsets was found in patients with PM, a disease with a predominantly localized nature. However, the lack of correlation between cancer stage and the number or the function of peripheral Treg cells in LC patients refuted the hypothesis that these cells are involved in tumor spreading. A possible involvement of the peripheral Treg cell pool in cancer development and/or in inducing systemic immunosuppression in LC patients can be hypothesized.

Keywords: lung cancer; pleural mesothelioma; CD4⁺CD25⁺; CD4⁺CD25^high; CD8⁺CD28⁺; T regulatory cells

Abbreviations: APCs: antigen-presenting cells; ELISA: enzyme-linked immunosorbent assay; LC: lung cancer; MoAbs: monoclonal antibodies; NHC: normal healthy controls; NSCLC: non-small-cell lung cancer; PM: pleural mesothelioma; SCLC: small cell lung cancer; TILs: tumor-infiltrating T lymphocytes; Treg cells: T regulatory cells; TNM: tumor size nodal involvement metastases.