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Updated: Nov 24, 2025
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Defects at the Posttranscriptional Level Account for the Low TCRζ Chain Expression Detected in Gastric Cancer
Ana Aguinaga-Barrilero1, Patricia Castro-Sánchez1, Ignacio Juárez1
1Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
Background:
Reduced TCRζ chain surface has been reported in T cells from patients with different inflammatory conditions and cancer. However, the causes of this diminished expression in cancer remain elusive.
Methods:
T cell-enriched populations of blood or tissue (tumoral and nontumoral) origin from 44 patients with gastric adenocarcinoma and 33 healthy subjects were obtained. Samples were subjected to cytofluorimetry, Western blot analysis, TCRζ cDNA sequencing experiments, measurement of TCRζ mRNA levels, and caspase-3 activity assays.
Results:
Cytofluorimetry revealed a decreased TCRζ expression in T cells of patients, assessed either as percentage of cells expressing this chain (blood: control subjects 99.8 ± 0.1%, patients 98.8 ± 1.1%P < 0.001; tissue: control subjects 96.7 ± 0.9%, patients tumoral tissue 67.9 ± 27.0%, patients nontumoral tissue 82.8 ± 12.6%, P = 0.019) or mean fluorescence intensity (MFI) value (blood: control subjects 102.2 ± 26.0; patients 58.0 ± 12.3, P = 0.001; tissue: control subjects 99.4 ± 21.4; patients tumoral tissue 41.6 ± 21.4; patients nontumoral tissue 62.3 ± 16.6, P = 0.001). Other chains pertaining to the TCR-CD3 complex (CD3ε) showed no significant differences (MFI values). Subsequent TCRζ cDNA sequencing experiments or measurements of TCRζ mRNA levels disclosed no differences between patients and control subjects. Evaluation of caspase-3 activity showed higher levels in T cell extracts of patients, and this activity could be decreased by 70% with the use of the inhibitor Ac-DEVD-FMK, although CD3ζ expression levels did not recover.
Conclusions:
These results further place the defect responsible for the low TCRζ expression in cancer at the posttranscriptional level and suggests contrary to what has been proposed in other pathologies that elevated caspase-3 activity is not the causative agent.
Insights
Reduced T cell receptor zeta (TCRζ) chain expression in gastric cancer patients is not due to genetic or mRNA changes. Elevated caspase-3 activity does not cause this diminished TCRζ expression.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Diminished T cell receptor zeta (TCRζ) chain surface expression is observed in T cells of patients with inflammatory conditions and cancer.
- The underlying mechanisms causing reduced TCRζ expression in cancer remain unclear.
Purpose of the Study:
- To investigate the causes of reduced TCRζ expression in T cells from gastric adenocarcinoma patients.
- To determine if elevated caspase-3 activity contributes to the diminished TCRζ expression.
Main Methods:
- Analysis of T cell-enriched populations from gastric cancer patients and healthy controls using flow cytometry and Western blot.
- TCRζ cDNA sequencing and mRNA level measurements were performed.
- Caspase-3 activity assays were conducted, with and without caspase-3 inhibitor.
Main Results:
- T cells from gastric cancer patients showed significantly decreased TCRζ expression in both blood and tumor tissues compared to controls.
- No significant differences in TCRζ cDNA or mRNA levels were found between patients and controls.
- Elevated caspase-3 activity was observed in T cells from patients, but inhibiting it did not restore TCRζ expression.
Conclusions:
- The defect causing low TCRζ expression in gastric cancer occurs at the posttranscriptional level.
- Elevated caspase-3 activity is not the primary cause of diminished TCRζ expression in this cancer context.
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