Progressive changes in composition of lymphocytes in lung tissues from patients with non-small-cell lung cancer

// Maria del Mar Valenzuela-Membrives 1 , Francisco Perea-Garcia 3 , Abel Sanchez- Palencia 2 , Francisco Ruiz-Cabello 3 , Mercedes Gomez-Morales 4 , Maria Teresa Miranda-Leon 5 , Inmaculada Galindo-Angel 4 , Maria Esther Farez-Vidal 6 1 Department of Pneumology, San Cecilio University Hospital, Granada, Spain 2 Department of Thoracic Surgery, Virgen de las Nieves University Hospital, Granada, Spain 3 Institute for Biomedical Research, Virgen de las Nieves University Hospital, Granada, Spain 4 Department of Pathology, School of Medicine, University of Granada, Granada, Spain 5 Department of Statistics and Operative Research, School of Medicine, University of Granada, Granada, Spain 6 Department of Biochemistry and Molecular Biology, School of Medicine, University of Granada, Granada, Spain Correspondence to: Maria Esther Farez-Vidal, email: efarez@ugr.es Keywords: immunological response, lung cancer, immunohistochemistry, flow cytometry, lymphocyte subsets Received: May 18, 2016      Accepted: September 19, 2016      Published: September 26, 2016 ABSTRACT Immune cell infiltration is a common feature of many human solid tumors. Innate and adaptative immune systems contribute to tumor immunosurveillance. We investigated whether tumors evade immune surveillance by inducing states of tolerance and/or through the inability of some immune subpopulations to effectively penetrate tumor nests. Immunohistochemistry and flow cytometry analysis were used to study the composition and distribution of immune subpopulations in samples of peripheral blood, tumor tissue (TT), adjacent tumor tissue (ATT), distant non-tumor tissue (DNTT), cancer nests, cancer stroma, and invasive margin in 61 non-small-cell lung cancer (NSCLC) patients. A significantly higher percentage of T and B cells and significantly lower percentage of NK cells were detected in TT than in DNTT. Memory T cells (CD4 + CD45RO + , CD8 + CD45RO + ) and activated T cells (CD8 + DR + ) were more prevalent in TT. Alongside this immune activation, the percentage of T cells with immunosuppressive activity was higher in TT than in DNTT. B- cells were practically non-existent in tumor nests and were preferentially located in the invasive margin. The dominant NK cell phenotype in peripheral blood and DNTT was the cytotoxic phenotype (CD56 + CD16 + ), while the presence of these cells was significantly decreased in ATT and further decreased in TT. Finally, the immunologic response differed between adenocarcinoma and squamous cell carcinoma and according to the tumor differentiation grade. These findings on the infiltration of innate and adaptative immune cells into tumors contribute to a more complete picture of the immune reaction in NSCLC.