Related Experiment Video
Updated: Feb 17, 2026
Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
Tumor-infiltrating CD4+ T cells in patients with gastric cancer
Long Yuan1, Benling Xu2, Peng Yuan1
1Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan People's Republic of China.
Background:
T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients.
Materials And Methods:
Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China. Phenotypic analysis based on isolation of tumor-infiltrating lymphocytes and intracellular IFN-γ staining assay is conducted. Statistical analysis is performed to show significance.
Results:
The results showed that the percentage of CD4+ T-cells among CD3+ cells in tumors was significantly higher than that in the matched paraneoplastic tissue. CD4+ CD25high CD127low regulatory T-cells (Tregs), PD-1+, Tim-3+, and PD-1+ Tim-3+ cells were up-regulated on tumor infiltrating T-cells from patients with GC compared to their expressions on corresponding peripheral blood and peritumoral T-cells. Blockades of PD-1+ and Tim-3+ were effective in restoring tumor infiltrating T-cells' production of interferon-gamma (IFN-γ). Combined PD-1+ and Tim-3+ inhibition had a synergistic effect on IFN-γ secretion by CD4+ T-cells.
Conclusion:
The results suggested that the composition, inhibitors, and location of the immune infiltrate should be considered when evaluating antitumor immunotherapy. A new insight into the mechanisms underlying T cell dysfunction is provided.
Insights
In gastric cancer, CD4+ T-cells accumulate in tumors, exhibiting inhibitory phenotypes like PD-1 and Tim-3. Blocking these markers enhances anti-tumor immunity by restoring T-cell function.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- T lymphocytes are crucial for anti-viral and anti-tumor immunity.
- The role of inhibitory molecules and cytokines on tumor-infiltrating CD4+ T-cells in gastric cancer (GC) is not well understood.
- This study investigates T-cell subsets, differentiation, and inhibitory phenotypes in GC patients' blood and tissues.
Purpose of the Study:
- To analyze the distribution of T-cell subsets in gastric cancer.
- To characterize the differentiation and inhibitory phenotype of tumor-infiltrating T-cells.
- To evaluate the impact of inhibitory molecules on T-cell function in GC.
Main Methods:
- Patient enrollment and sample collection from GC patients (2014-2015).
- Phenotypic analysis of tumor-infiltrating lymphocytes.
- Intracellular interferon-gamma (IFN-γ) staining assay and statistical analysis.
Main Results:
- CD4+ T-cells were significantly increased in tumors compared to paraneoplastic tissue.
- Upregulation of regulatory T-cells (Tregs), PD-1+, Tim-3+, and PD-1+Tim-3+ cells on tumor-infiltrating T-cells.
- Blockade of PD-1 and Tim-3 restored IFN-γ production; combined inhibition showed synergistic effects.
Conclusions:
- Immune infiltrate composition, inhibitors, and location are critical for evaluating anti-tumor immunotherapy.
- Provides new insights into mechanisms of T-cell dysfunction in gastric cancer.
- Suggests potential therapeutic strategies targeting inhibitory molecules on T-cells.
