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Central European Journal of Immunology
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vol. 38

Clinical immunology
Peripheral blood levels of cellular and humoral immunity parameters in esophageal and gastric cancer patients

Huseyin Begenik
Mehmed Kursad Turkdogan
Ahmet Cumhur Dulger
Mehmet Naci Aldemir
Ramazan Esen
Rafet Mete

(Centr Eur J Immunol 2013; 38 (3): 355-357)
Online publish date: 2013/10/28
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Carcinogenesis is related to several factors such as genetic abnormalities, diet, lifestyle, and immune deficiencies [1-6]. Cancer patients have different immune responses. Tumor-induced immunosuppression is the main problem in cancer cell biology [7, 8]. In the case of cancer, many immunologic alterations occur in the lymphocyte sub-groups including CD4, CD8, B-lymphocytes and natural killer (NK) cells. If patients with cancer have impaired lymphocyte functions, the prognosis is usually poor [9].

Patients with gastrointestinal cancer have also immune system alterations including decreased T-cells proliferation and CD4/CD8 ratio, and diminished T-helper cell cytokine production [10].

In this study, we aimed to investigate the changes of humoral and cell-mediated immune system functions involving peripheral blood lymphocyte groups and sub-groups in patients with newly diagnosed esophageal and stomach cancer.

Material and methods

In this study, we recruited 40 patients with newly diagnosed esophageal cancer (20 of them) or stomach cancer (20 of them), while age-matched 20 healthy individuals were recruited as a control group. The diagnosis of cancer was made by histopathologic examination of the endoscopic biopsy materials. The patients who were previously diagnosed with cancer or received any cancer-related treatment such as surgery, chemotherapy, or radiotherapy were excluded from the study.

CD3, CD4, CD8, CD4/CD8 ratio, CD 19 and NK cell’s antigens (CD3–, CD16+, and CD56+) were studied in all cases. For this purpose, 2 cc blood samples were collected into the standard cell count tubes with ethylene diamine tetraacetic acid (EDTA). Red blood cells were eliminated from the samples with immunoprep solution using Coulter Q-Prep device. Subsequently, 100 µl of the yielded solutions containing mononuclear cells were mixed with 20 µl of the combination of the antihuman antiCD3 IgG1 (FITC), antiCD4 IgG1 (FITC), antiCD8 IgG1 (PE), antiCD16 IgG1 (PE), antiCD19 IgG1 (PE) and antiCD56 IgG1 (PE) monoclonal antibodies. Then, positive cells were counted with a flow cytometry device (Coulter Epics XL).

Statistical data analysis was performed with SPSS 15.0 software program. The yielded data including age, CD3, CD4, CD8, CD4/CD8, CD19 and NK cells were correlated with the cancer types and sex with factorial variance analyses (Factorial ANOVA). The factorial analysis of variance was used to analyze the interactive effects of multiple categorical independent variables. When significant differences among main effects were observed using ANOVA, Duncan’s multiple range test was used to determine differences among individual means.


Twenty patients with esophageal cancer (15 females, 5 males), 20 patients with stomach cancer (8 females, 12 males), and 20 healthy individuals (12 females, 8 males) as controls were included in the study. The mean age of the patients with esophageal cancer was 59.2 ±1.98 years, patients with stomach cancer – 63.9 ±2.45 years, and control group – 55.3 ±2.30 years. There were no statistically significant differences in the age group and gender. Among patients suffering from esophageal cancer, 18 of them (90%) had squamous cell carcinoma, and 2 patients (10%) had adenocarcinoma. Esophageal cancer was located on the upper third of esophagus in 3 patients (15%), median third of esophagus in 4 patients (20%), and lower third of esophagus in 13 patients (65%). All stomach cancer patients had adenocarcinoma.

As to the localization of cancer in the stomach, 2 of them (10%) were diffuse, 3 of them (15%) were in the cardia, 8 of them (40%) were in the corpus, and 7 (35%) were in the antrum.

The CD3 and CD8 ratios were significantly higher in the patients with esophageal cancer (p = 0.012, p = 0.003, respectively) and the ratio of the NK cells was significantly higher in the patients with stomach cancer (p = 0.001) when compared to the control groups. The ratio of CD19 was significantly lower in the two cancer groups (p = 0.031). There were no significant differences in the ratio of CD4 and CD4/CD8 between the groups (Table 1). No correlation between the stage of cancer and the ratio of CD cells was detected.


Patients with gastric carcinoma usually have an impaired immune system involving decreased cell-mediated immune response [11, 12]. Hong et al. found that the ratio of CD3, CD4, CD8, CD16 and CD19 were lower and the ratio of CD4/CD8 was higher in the patients with gastric cancer than the control group. These results can be associated with better survival [13]. In another study, the humoral and cell-mediated immunity showed variation according to the stage of the cancer [14]. Barbieri et al. found a low CD8 ratio in patients with gastric cancer [15]. On the other hand, Yao et al.’s study showed a high CD8 ratio in patients with gastric cancer. Additionally, they demonstrated that the expression of the human telomerase catalytic subunit (hTERT) was significantly higher in the pre-cancerous lesions of the immunocompromised patients. In the early stage of the gastric cancer, the expression of the hTERT was significantly increased; meanwhile, cellular-mediated immunity was decreased. It was postulated that a telomerase activity would play a critical role in the pathogenesis of gastric cancer [16].

Another study on the correlation between the immunological assessment of the gastric tumor tissue and the tumor prognosis showed that patients with high NK cells had better prognosis. Thus, the postoperative close monitoring is very important for gastric cancer patients with low NK cell infiltration into the tumor tissue [17]. In another similar study, there were no differences in the ratio of T-lymphocytes and NK cells between the patients with gastric cancer and the control group; however, the NKG2D expression of the NK cells was significantly lower in the cancer group. Therefore, it was proposed that the NKG2D in NK might play a critical role in anti-tumor activity [18].

The ratios of CD3+CD8+ and CD8+CD25+ T cells were found to be significantly lower in patients with esophageal cancer; however, the ratio of CD4+CD25+ T cells and the ratio of CD4/CD8 were found to be significantly higher in the same group [19]. It was also shown that there was a direct relation between the esophageal cancer prognosis and the ratio of CD4 and CD8 cells; though there was no correlation between the ratio of NK cells and the prognosis. In addition, the combined immunotherapy containing active CD4 and CD8 T cells was shown to be effective in the treatment of the patients with squamous cell esophageal carcinoma [20].

In one study evaluating both patients with gastric cardia and esophageal cancer, the operability of cancer patients was linked to the subgroups of T (CD3) and B (CD19) cells; the high CD4+CD25+ T cells ratio was correlated with poor prognosis [21].

In our study, the high level of T lymphocytes in esophageal cancer and the high ratio of the NK cells in the stomach cancer (both T cell and NK cell are parameters for cell-mediated immunity) would suggest that different etiological and immunological mechanisms might play a key role in these cancer types. In addition, the diminished humoral immune responses (insufficient formation of antibodies) in both cancer groups would be evidence for an impaired body response to the tumor cells (Table 2).

In conclusion, understanding of the cancer immunology of esophageal and stomach cancer will provide insight into the pathogenesis of the cancer. Therefore, further and extensive cancer immunology studies should be conducted to develop new diagnostic strategies in patients with upper gastrointestinal tract cancer.

The authors declare no conflict of interests.


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Copyright: © 2013 Polish Society of Experimental and Clinical Immunology This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
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