The role of the immune system in non-small cell lung carcinoma and potential for therapeutic intervention

Sex hormones are included in many physiological and pathological pathways. Estrogens belong to steroid hormones active in female sex. Estradiol (E2) is the strongest female sex hormone and, with its receptors, contributes to oncogenesis, cancer progression and response to treatment. In recent years, a role of immunosurveillance and suppression of immune response in malignancy has been well defined, forming the basis for cancer immunotherapy. The interplay of sex hormones with cancer immunity, as well as the response to immune checkpoint inhibitors, is of interest. In this review, we investigate the impact of sex hormones on natural immune response with respect to main active elements in anticancer immune surveillance: dendritic cells, macrophages, lymphocytes and checkpoint molecules. We describe the main sex-dependent tumors and the contribution of estrogen in their progression, response to treatment and especially modulation of anticancer immune response.

Regulatory T cells (Tregs) play an important role in the suppression of the immune response in lung cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed on T lymphocytes is capable of downregulating cytotoxic T cells and is constitutively expressed on Tregs. Little is known about the population of Tregs with two forms of CTLA-4: surface (s) and intracellular (in) in the lung cancer environment. Th17 cells defined by production of IL-17 have pleiotropic functions in anticancer immune response. Our aim was to detect the elements of immune response regulation in lung cancer in three compartments: by analysis of bronchoalveolar lavage fluid (BALF) from the lung affected by cancer (clBALF), healthy symmetrical lung (hlBALF) and peripheral blood (PB) from the same patient. A total of 54 samples were collected. Tregs, (s)CTLA-4, (in)CTLA-4 were detected by flow cytometry with antibodies against CD4, CD25, Foxp3, CD127, CTLA-4, and concentration of IL-17 was estimated by ELISA. We observed a significantly higher proportion of Tregs in clBALF than in hlBALF or PB (8.5 vs. 5.0 vs. 5.1%, respectively, p < 0.05). The median proportion of (in)CTLA-4+ Tregs was higher in clBALF than in hlBALF or PB (89.0, 81.5, 56.0%, p < 0.05). IL-17 concentration was the highest in clBALF—6.6 pg/ml. We observed a significant correlation between the proportion of Tregs and (in)CTLA-4+ Tregs with IL-17A concentration in clBALF. We confirmed significant differences in the proportion of regulatory elements between cancerous lung and healthy lung and PB and the usefulness of BALF analysis in evaluation of immune response regulation in local lung cancer environment.

Mechanisms of immune response regulation in lung cancer

Background. Obstructive sleep apnoea syndrome (OSAS) brings risk of serious complications. The study objective was to assess elements of the cellular immune response in the course of OSAS. Methods. Peripheral blood (PB) lymphocytes: T, B, NK, NKT‐like, Th, Tc, and HLA DR+ T cells were evaluated by flow cytometry of 48 OSA patients; the concentration of adiponectin, interleukin 1β, and TNFα was measured by ELISA method. The OSA complication score was developed and used for statistical analysis. Results. The proportion of B cells and Th/Tc ratio were significantly lower in the BP of OSA patients when compared with control subjects (median 7.9 versus 10.9%, 0.9 versus 1.5, p < 0.05). The proportion of Tc, NK, NKT‐like, and HLADR positive T cells were elevated in OSA patients when compared with healthy subjects (36.4 versus 26.8, 15.5 versus 8.5, 5.7 versus 3.0, and 8.4 versus 4.5%, p < 0.05, resp.) and were more pronounced in patients with metabolic syndrome. The grade of OSA complication score correlated with systemic inflammation markers and the proportion of B cells. The value of adiponectin/BMI ratio correlated significantly with SpO₂ (r = 0.31, p < 0.05), CRP (r = −0.35, p < 0.05), TNFα concentration (r = −0.36, p < 0.05), and proportion of B cells (r = 0.32, p < 0.05). Conclusion. Lymphocytes B, Tc, NK, NKT‐like, and adiponectin are involved in systemic immune response in OSA patients possibly predisposing them to cardiovascular and metabolic complications.