Alteration of Signal-Transducing Molecules and Phenotypical Characteristics in Peripheral Blood Lymphocytes from Gastric Carcinoma Patients

Abstract

The mechanisms underlying the impaired immune response frequently observed in cancer patients are not fully understood. Alteration of T-cell-associated signal transduction molecules has recently been implicated in immune suppression in tumor-bearing hosts. Furthermore, T cells from tumor-bearing host, irrespective of the presence of the ζ-chain, showed a lack of proliferative activity and cytotoxic function. In the present study, we investigated the expression of the ζ-chain molecule and the p56^lck and p59^fyn protein tyrosine kinase (PTK) levels in peripheral blood T lymphocytes (T-PBL) from patients with advanced gastric carcinomas; for this, flow cytometric analysis and immunoblotting, respectively, were used. We also compared the results of flow cytometric analysis of PBL between stomach cancer patients and normal healthy volunteers. In T-PBL from 22 tumor-bearing hosts, significantly reduced ζ-chain expression (16/22, 73%) was observed. Moreover, the expression level of p56^lck in T-PBL from patients was significantly lower than that of p59^fyn. Flow cytometric analysis of T-PBL indicated a markedly increased CD8+28– cell population in T-PBL from 19 tumor-bearing hosts.

A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis

“…Our finding that Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), by triggering oxygen radical formation in monocytes, induced the disappearance of CD3ζ from lymphocytes suggests that this peptide may contribute to lymphocyte dysfunction in gastric adenocarcinoma. It is noteworthy that changes typical for lymphocytes recovered from patients with invasive gastric carcinomas, such as CD3ζ downmodulation and apoptosis (23,39), were induced by the Hp(2-20) peptide in vitro. However, it should be emphasized that further studies are needed to clarify the putative role of Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) in gastric carcinogenesis.…”

Pattern-Recognition Receptors and Gastric Cancer

“…Release of DAMPs, which are especially targeted by TLR2 and TLR4 (140–145) during cancer progression may cause chronic inflammation leading to down-regulation of the ζ chain of the T-cell and NK cell activating receptors [for comprehensive information on this topic see the review by Baniyash et al (146)], which entails T-cell and NK cell dysfunction, a phenomenon observed in some malignancies such as GC (147, 148), colon (149), prostate (150), cervical (151), and pancreatic cancer (152). In addition to immunosuppression, DAMPS appear to facilitate other processes during gastric carcinogenesis.…”

Fluorescent Biomarker in Colorectal Cancer

“…For example, colorectal cancer patients have abnormal plasma and erythrocyte fatty acid levels, as well as of their polyunsaturated metabolites (Robinson et al, 2001). Ultimately, in lymphocytes, because membrane physicochemical status and cell lipid metabolism play pivotal roles in signal transduction pathway(s) activities important in maintaining cell function (Kim et al, 1999), it would not be unexpected that disturbances in these parameters could result in altered immunocompetence in hosts with these affected cells. Fluorescence intensity of ABM in lymphocytes suspension tended to decrease with progression of cancer.…”