Membrane (CD8⁺PD-1⁺ and CD4+PD-1⁺) and soluble (sPD-1 and sPD-L1) forms of immune checkpoints in melanoma, breast cancer, and oral mucosal cancer patients: A observational study

Abstract

Background. The PD-1/PD-L1 pathway plays an important role in tumor evasion from immunological surveillance. In addition to the membrane forms of PD-1 and PD-L1, there are soluble variants: sPD-1 and sPD-L1. Both membrane and soluble forms have immunoregulatory properties and can affect the function and number of different immune cell populations. Aim. To study the relationship between the initial level of CD8⁺PD-1⁺ and CD4+PD-1⁺ lymphocytes and soluble forms of sPD-1 and sPD-L1 with the percentage of the main effector and regulatory populations of peripheral blood (PB) lymphocytes and tumor-infiltrating lymphocytes. Materials and methods. The study included melanoma, breast cancer and the oral mucosa cancer patients. The percentage of cell populations of PB lymphocytes and tumor-infiltrating lymphocytes was determined by flow cytometry before treatment. The concentrations of sPD-1 and sPD-L1 proteins were studied in blood serum using enzyme immunoassay. Results. The relationship of the level of CD8⁺PD-1⁺ cells with certain populations of CD8-lymphocytes in PB and tumor tissue was found. In the PB of melanoma patients with CD8⁺CD11b⁺CD28⁺ and CD8⁺CD11b⁻CD28⁻ T cells, in breast cancer patients with a population of CD8⁺CD11b⁺CD28⁺ lymphocytes. In the tumor tissue of all patients there was a positive correlation with a population of regulatory CD8⁺CD11b⁻CD28⁻ T cells. The immunoregulatory properties of sPD-1 and sPD-L1 were confirmed. Both sPD-1 and sPD-L1 levels were positively correlated with the number of suppressor CD8⁺CD11b⁻CD28⁻ T cells and negatively with the level of CD8 lymphocytes, CD8⁺CD11b⁺CD28⁺ cytotoxic/memory T cells, B cells and activated CD25 lymphocytes. Conclusion. The results of the study can make a certain contribution to the study of the prognostic significance of membrane and soluble forms of PD-1 and PD-L1, taking into account the peculiarities of their relationship with suppressor and effector populations of lymphocytes of systemic and local immunity.