The prognostic significance of HLA-A2 expression on somatic cells in patients with left-sided colon and rectal cancers

Introduction. Current knowledge about colorectal cancer (CRC) identifies tumor immunogenicity as one of the more important issues. In cancers, a prerequisite for immune system activation is the presentation of tumor associated antigen (TAA) epitopes to immunocompetent cells. HLA-A2 is one of the antigens in the context of which TAAs are present, but data on the possible impact of HLA-A2 antigen expression on the survival of patients with colorectal cancer are scarce and sometimes contradictory. The aim of this study was to analyse the relationship between HLA-A2 expression in patients with left-sided colorectal cancer in various stages of disease and their long-term survival, and to answer the question of whether a lack of HLA-A2 expression is actually a negative prognostic factor. Material and methods.  A prospective analysis of 58 patients with left-sided colorectal cancer was carried out. Expression of HLA-A2 was determined by patient blood lymphocyte staining, and analysed using flow cytometry. Results. In the study group, patients with HLA-A2 expression lived statistically longer than HLA-A2 negative patients (p = 0.027). There was no significant difference in overall survival between the HLA-A2+ and HLA-A2- groups with stage II and III left-sided CRC. However, the Cox proportional hazard model showed that a lack of HLA-A2 expression was a negative prognostic factor in the group of radically operated patients without distant metastases. Conclusions. HLA-A2 status may affect the clinical course of patients with left-sided colon and rectal cancer, although left-sided tumors are less immunogenic than right-sided ones. HLA-A2-positive patients with left-sided colorectal cancer lived statistically longer than those who were HLA-A2-negative (p = 0.027). Lack of HLA-A2 expression was a negative prognostic factor in the group of radically operated patients

Properties of monocytes generated from haematopoietic CD34+ stem cells from bone marrow of colon cancer patients

Monocytes exhibit direct and indirect antitumour activities and may be potentially useful for various forms of adoptive cellular immunotherapy of cancer. However, blood is a limited source of them. This study explored whether monocytes can be obtained from bone marrow haematopoietic CD34(+) stem cells of colon cancer patients, using previously described protocol of expansion and differentiation to monocytes of cord blood-derived CD34(+) haematopoietic progenitors. Data show that in two-step cultures, the yield of cells was increased approximately 200-fold, and among these cells, up to 60 % of CD14(+) monocytes were found. They consisted of two subpopulations: CD14(++)CD16(+) and CD14(+)CD16(−), at approximately 1:1 ratio, that differed in HLA-DR expression, being higher on the former. No differences in expression of costimulatory molecules were observed, as CD80 was not detected, while CD86 expression was comparable. These CD14(+) monocytes showed the ability to present recall antigens (PPD, Candida albicans) and neoantigens expressed on tumour cells and tumour-derived microvesicles (TMV) to autologous CD3(+) T cells isolated from the peripheral blood. Monocytes also efficiently presented the immunodominant HER-2/neu(369–377) peptide (KIFGSLAFL), resulting in the generation of specific cytotoxic CD8(+) T lymphocytes (CTL). The CD14(++)CD16(+) subset exhibited enhanced cytotoxicity, though nonsignificant, towards tumour cells in vitro. These observations indicate that generation of monocytes from CD34(+) stem cells of cancer patients is feasible. To our knowledge, it is the first demonstration of such approach that may open a way to obtain autologous monocytes for alternative forms of adaptive and adoptive cellular immunotherapy of cancer

The prognostic significance of HLA-A2 expression on somatic cells in patients with left-sided colon and rectal cancers

Introduction. Current knowledge about colorectal cancer (CRC) identifies tumor immunogenicity as one of the more important issues. In cancers, a prerequisite for immune system activation is the presentation of tumor associated antigen (TAA) epitopes to immunocompetent cells. HLA-A2 is one of the antigens in the context of which TAAs are present, but data on the possible impact of HLA-A2 antigen expression on the survival of patients with colorectal cancer are scarce and sometimes contradictory. The aim of this study was to analyse the relationship between HLA-A2 expression in patients with left-sided colorectal cancer in various stages of disease and their long-term survival, and to answer the question of whether a lack of HLA-A2 expression is actually a negative prognostic factor. Material and methods.  A prospective analysis of 58 patients with left-sided colorectal cancer was carried out. Expression of HLA-A2 was determined by patient blood lymphocyte staining, and analysed using flow cytometry. Results. In the study group, patients with HLA-A2 expression lived statistically longer than HLA-A2 negative patients (p = 0.027). There was no significant difference in overall survival between the HLA-A2+ and HLA-A2- groups with stage II and III left-sided CRC. However, the Cox proportional hazard model showed that a lack of HLA-A2 expression was a negative prognostic factor in the group of radically operated patients without distant metastases. Conclusions. HLA-A2 status may affect the clinical course of patients with left-sided colon and rectal cancer, although left-sided tumors are less immunogenic than right-sided ones. HLA-A2-positive patients with left-sided colorectal cancer lived statistically longer than those who were HLA-A2-negative (p = 0.027). Lack of HLA-A2 expression was a negative prognostic factor in the group of radically operated patients.Introduction. Current knowledge about colorectal cancer (CRC) identifies tumor immunogenicity as one of the more important issues. In cancers, a prerequisite for immune system activation is the presentation of tumor associated antigen (TAA) epitopes to immunocompetent cells. HLA-A2 is one of the antigens in the context of which TAAs are present, but data on the possible impact of HLA-A2 antigen expression on the survival of patients with colorectal cancer are scarce and sometimes contradictory. The aim of this study was to analyse the relationship between HLA-A2 expression in patients with left-sided colorectal cancer in various stages of disease and their long-term survival, and to answer the question of whether a lack of HLA-A2 expression is actually a negative prognostic factor. Material and methods. A prospective analysis of 58 patients with left-sided colorectal cancer was carried out. Expression of HLA-A2 was determined by patient blood lymphocyte staining, and analysed using flow cytometry. Results. In the study group, patients with HLA-A2 expression lived statistically longer than HLA-A2 negative patients (p = 0.027). There was no significant difference in overall survival between the HLA-A2+ and HLA-A2- groups with stage II and III left-sided CRC. However, the Cox proportional hazard model showed that a lack of HLA-A2 expression was a negative prognostic factor in the group of radically operated patients without distant metastases. Conclusions. HLA-A2 status may affect the clinical course of patients with left-sided colon and rectal cancer, although left-sided tumors are less immunogenic than right-sided ones. HLA-A2-positive patients with left-sided colorectal cancer lived statistically longer than those who were HLA-A2-negative (p = 0.027). Lack of HLA-A2 expression was a negative prognostic factor in the group of radically operated patients.

T-regulatory lymphocytes in peripheral blood of gastric and colorectal cancer patients

AIM: To assess the absolute number of T-regulatory cells (Tregs; CD4+CD25+Foxp3+) in the peripheral blood of gastric and colorectal cancer patients