627P - Immune status of patients with different stages of colorectal cancer with and without circulating tumour cells

Abstract

BackgroundOur purpose was to study parameters of the cellular immunity in patients with different stages of colorectal cancer with and without circulating tumor cells (CTCs). MethodsThe presence of CTCs and parameters of the cellular immunity were studied in 60 colorectal cancer (CRC) patients: stage II – 20, stage III – 12, stage IV – 28 patients, adenocarcinoma in all cases. Blood levels of CTCs were determined before the treatment using the CellSearch System (Janssen Diagnostics, LLC) with iron microparticles coated with antibodies to epithelial cell adhesion markers EpCAM, CD45 and cytokeratins 8,18,19. Subpopulations of lymphocytes were studied using the FACSCantoII flow cytometer (BD): percentage of T-B-NК-cells, Tregs; activated CD4+ and CD8+ cells, naive T-lymphocytes and memory T cells; expression of CD335, perforin and granzyme B was evaluated in NК cells. ResultsThe results revealed a number of differences in immunological parameters in patients with and without CTCs. Stage II CRC with CTCs showed statistically significantly higher content of lymphocytes (19.1±2.7 vs 15.6±1.4%), CD335+ NK cells (44.9±7.6 vs 19.2±4.0%) and the respiratory burst index in granulocytes (97.5±1.6 vs 92.3±1.2%); p<0.05 in all cases. Stage III CRC with CTCs was characterized by decreased lymphocyte and monocyte levels, while granulocyte content increased. These patients demonstrated elevated levels of CD4+ cells with early and late activation markers: CD38+ and HLA-DR+ by 2 times, CD25+ by 6 times, p<0.05 in all cases. CTC-positive patients with stage IV CRC, compared to CTC-negative ones, showed lower levels of NK cells (16.6±2.0 vs 28.4±5.5%), CD4+CD69+(5.1±0.8 vs 8.2±1.0%), and CD8+CD25+(2.8±0.48 vs 5.5±1.1%; p<0.05). ConclusionsCTCs in locally advanced CRC is associated with stimulation of functional parameters of innate immunity and activated Th, while in metastatic CRC - with inhibition of cytotoxic lymphocytes of innate and adaptive immunity, which, apparently, is associated with poor prognosis. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.