Quantification of Blood Dendritic Cells in Colorectal Cancer Patients During the Course of Disease

Abstract

Colorectal cancer is a malignancy with poor prognosis that might be associated with defective immune function. The aim of the present study was to investigate circulating dendritic cells in colorectal cancer patients, in order to contribute to elucidate tumor-escape mechanisms and to point out a possible correlation with the clinical condition of the disease. Therefore, we enumerated ex vivo myeloid and plasmacytoid dendritic cells, through multicolor flow cytometry, in 26 colorectal patients and 33 healthy controls. Furthermore we performed several analyses at determined time points in order to define the immunological trend of cancer patients after surgery and other conventional treatments. At the pre-operative time point the absolute number of plasmacytoid dendritic cells in cancer patients was significantly reduced in comparison to controls, this result being mainly referred to stage III-IV patients. The number of myeloid dendritic cells did not show any significant difference compared to healthy controls; interestingly the expression of the tolerogenic antigen CD85k was significantly higher on cancer patients' myeloid dendritic cells than controls'. At the following samplings, circulating dendritic cell absolute number did not show any difference compared to controls. Conclusively the impairment of the number of circulating dendritic cells may represent one of the tumor escape mechanisms occurring in colorectal cancer. These alterations seem to be correlated to cancer progression. Our work sheds light on one of dendritic cell-based tumor immune escape mechanisms. This knowledge may be useful to the development of more effective immunotherapeutic strategies.

Immunoglobulin-like transcript 3 is expressed by myeloid-derived suppressor cells and correlates with survival in patients with non-small cell lung cancer

“…The relevance of ILT3 in cancer patients is supported by results from the literature 14,37,38 and therefore further investigation of its mode of action should be performed. Nonetheless, it is debatable whether ILT3 on its own would determine the immunosuppressive status of MDSCs; rather, the sum of all immunosuppressive mechanisms and their relative contribution to the activity of MDSC will probably determine the extent of its unfavorable effects in cancer patients.…”

“…10 An important mediator of the induction of immune tolerance is immunoglobulin-like transcript (ILT) 3 (also known as LILRB4, CD85k, or LIR-5), which is expressed on monocytes and antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs). 11,12 ILT3 expression marks tolerogenic DCs and has been reported to be elevated in APCs of cancer patients 13,14 and decreased in autoimmune diseases. 15,16 ILT3 is believed to signal via its immunoreceptor tyrosine-based inhibitory motifs (ITIMs).…”

Role of prostanoids in gastrointestinal cancer

“…The studies evaluating levels of circulating cDCs and pDCs in CRC patients have resulted in conflicting data. One report showed that the levels of pDCs, but not cDCs, in blood were reduced in CRC patients (138). In contrast, another study showed that levels of both circulating cDCs and pDCs were reduced in CRC patients (139).…”

LILRB receptor-mediated regulation of myeloid cell maturation and function

“…NSCLC patients with an increased LILRB4 high population had a shorter median survival than patients with a decreased LILRB4 high subset [55]. LILRB4 expression on conventional DC and pDCs was increased in colorectal cancer patients when compared to healthy controls [56]. While LILRB4 is down-regulated following DC activation [57], its expression is up-regulated on tolerogenic DCs, leading to the induction of Treg cells [58].…”