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.
Highlights
Lung cancer accounts for the largest number of cancer-related deaths worldwide, and more than 85% of cases are non-small-cell lung cancer (NSCLC)
Significant differences in NK cell, B cell, and T cell subsets were found between peripheral blood samples from NSCLC patients and healthy controls
A positive correlation was observed between the percentages of CD4+DR+, CD8+DR+, CD8+ CD45RO+, CD4+ CD39+, CD8+ CD39+ and CD4+ Treg subsets in the tumor sample and the percentages observed in peripheral blood
Summary
Lung cancer accounts for the largest number of cancer-related deaths worldwide, and more than 85% of cases are non-small-cell lung cancer (NSCLC). The localization, density, and/or functional orientation of different immune cell populations can be beneficial or deleterious for patients. Infiltrating immune cells can become activated through a perturbed phenotype and/or a functional profile that creates an environment conducive to T-cell suppression [10]. Regulatory T cells (Tregs) are a population of T cells that suppress the activation of the immune system and maintain immune tolerance to self-antigens. Tregs can contribute to immunosuppressive or antitumor activity, allowing tumors to evade the immune barrier in epithelial malignancies [11]. Potential mechanisms underlying the immunosuppressive effects of Tregs may include the production of inhibitory cytokines, such as TGF-β and IL-10, and the suppression of T cell function by competitive binding of interleukin-2 (IL-2) via cell surface receptor CD25 (IL-2 receptor). Several co-inhibitory molecules, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor receptor (GITR), bind to ligands on effector T cells and directly contribute to the inhibitory function of Tregs [14]
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