5205 - Immune status of patients with different stages of colorectal cancer with and without circulating tumor cells

Background

Our purpose was to study parameters of the cellular immunity in patients with different stages of colorectal cancer with and without circulating tumor cells (CTCs).

Methods

The 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.

Results

The 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).

Conclusions

CTCs 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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.